naphthoquinones and Adenocarcinoma

Napabucasin is a novel oral first-in-class cancer stemness inhibitor. Preclinical and early phase clinical trials showed promising antitumor efficacy signals for napabucasin in a variety of malignancies. In this article, we describe the design and rationale for the now completed BRIGHTER trial, a multicenter, randomized, placebo-controlled, Phase III study designed to determine the efficacy and safety of combining napabucasin with paclitaxel in previously treated patients with advanced gastric and gastroesophageal junction adenocarcinoma (NCT02178956). Patients were randomized in a 1:1 fashion to receive weekly paclitaxel with either napabucasin or placebo. The study failed to achieve its primary end point of overall survival in the intention to treat population. Ongoing analysis of the secondary end points includes progression-free survival, objective response rate, disease control rate, the safety of the combination therapy and evaluation of efficacy in the biomarker-positive subpopulation.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Benzofurans; Clinical Protocols; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Esophageal Neoplasms; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Naphthoquinones; Paclitaxel; Stomach Neoplasms; Survival Analysis; Treatment Outcome

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Topics: Adenocarcinoma; Bignoniaceae; DNA Damage; Humans; Molecular Structure; Naphthoquinones

Prognosis of pancreatic cancer patients remains extremely poor thus, the need for the development of new therapeutic options is crucial. Plumbagin, a naphthoquinone derivative from Plumbago indica has been found to possess various pharmacological properties including anticancer activity. The present study was designed to investigate the inhibitory potential of plumbagin and associated mechanisms in pancreatic cancer cells. Fluorescence and flow cytometric analysis exhibited an increased percentage of apoptotic cells in both monolayer culture and 3D tumor spheroids. Upon plumbagin treatment, reactive oxygen species content of the cancer cells escalated and prompted alleviation of the mitochondrial membrane potential, which triggers caspase-dependent apoptosis. Interestingly, N-acetylcysteine inhibited the plumbagin induced apoptosis. We also found that the expression of Bcl-2 protein decreased and the expression of Bax protein increased. Moreover, plumbagin treatment led to upregulation of cleaved caspase-3 and caspase-9. These results support the views that plumbagin induced stress signals by damaging mitochondria and induce ROS mediated apoptosis via intrinsic apoptotic signaling in pancreatic cancer cells. To summarize, our study suggests that plumbagin may be utilized as a future anti-cancer therapy agent against pancreatic cancer, which is a major threat owing to its stubborn intransigence towards current treatment regimens.

Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; DNA Damage; Humans; Membrane Potential, Mitochondrial; Mitochondria; Naphthoquinones; Oxidative Stress; Pancreatic Neoplasms; Reactive Oxygen Species; Signal Transduction

Plumbagin (PLB) is a phytochemical being used for centuries in traditional medicines. Recently, its capacity to inhibit the development of human tumors has been observed, through the induction of apoptosis, cell cycle arrest, and inhibition of angiogenesis and metastasis. Here we evaluated the mechanism of action of PLB in the kidney adenocarcinoma 786-O cell line, which are metabolizing cells important for toxicology studies. After the treatment with PLB, we observed increased apoptosis and cell cycle arrest in S and G2/M phases, starting at 5 µM. In addition, PLB was cytotoxic, genotoxic and induced loss of cell membrane integrity. Regarding gene expression, treatment with 7.5 µM PLB reduced the amount of MTOR, BCL2 and ATM transcripts, and increased CDKN1A (p21) transcripts. Phosphorylation levels of yH2AX was increased and MDM2 protein level was reduced following the treatment with PLB, demonstrating its genotoxic effect. Our results suggest that PLB acts in molecular pathways related to the control of proliferation and cell death in 786-O cells.

Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Autophagy; Cell Cycle Checkpoints; Cell Death; Cell Line, Tumor; Cell Proliferation; Cell Survival; Humans; Kidney Neoplasms; Naphthoquinones; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Phytochemicals; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases

Immunosuppressive myeloid-derived suppressor cells (MDSC) subvert antitumor immunity and limit the efficacy of chimeric antigen receptor T cells (CAR-T). Previously, we reported that the GM-CSF/JAK2/STAT3 axis drives liver-associated MDSC (L-MDSC) proliferation and blockade of this axis rescued antitumor immunity. We extended these findings in our murine liver metastasis (LM) model, by treating tumor-bearing mice with STAT3 inhibitors (STATTIC or BBI608) to further our understanding of how STAT3 drives L-MDSC suppressive function. STAT3 inhibition caused significant reduction of tumor burden as well as L-MDSC frequencies due to decrease in pSTAT3 levels. L-MDSC isolated from STATTIC or BBI608-treated mice had significantly reduced suppressive function. STAT3 inhibition of L-MDSC was associated with enhanced antitumor activity of CAR-T. Further investigation demonstrated activation of apoptotic signaling pathways in L-MDSC following STAT3 inhibition as evidenced by an upregulation of the pro-apoptotic proteins Bax, cleaved caspase-3, and downregulation of the anti-apoptotic protein Bcl-2. Accordingly, there was also a decrease of pro-survival markers, pErk and pAkt, and an increase in pro-death marker, Fas, with activation of downstream JNK and p38 MAPK. These findings represent a previously unrecognized link between STAT3 inhibition and Fas-induced apoptosis of MDSCs. Our findings suggest that inhibiting STAT3 has potential clinical application for enhancing the efficacy of CAR-T cells in LM through modulation of L-MDSC.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Benzofurans; Cell Line, Tumor; Colorectal Neoplasms; Cyclic S-Oxides; Drug Screening Assays, Antitumor; fas Receptor; Gene Expression Regulation, Neoplastic; Immunotherapy; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Targeted Therapy; Myeloid-Derived Suppressor Cells; Naphthoquinones; Neoplasm Proteins; Signal Transduction; Specific Pathogen-Free Organisms; STAT3 Transcription Factor; Tumor Burden; Tumor Escape

β,β-Dimethylacrylshikonin (DMAS) is an anti-cancer compound extracted from the roots of Lithospermum erythrorhizon. The present study aims to investigate the effects of DMAS on human lung adenocarcinoma cells in vitro and explore the mechanisms of its anti-cancer action. We showed that DMAS markedly inhibited cell viability in a dose- and time-dependent way, and induced apoptosis as well as autophagy in human lung adenocarcinoma cells. Furthermore, we found that DMAS stimulated endoplasmic reticulum stress and mediated autophagy through the PERK-eIF2α-ATF4-CHOP and IRE1-TRAF2-JNK axes of the unfolded protein response in human lung adenocarcinoma cells. We also showed that the autophagy induced by DMAS played a prosurvival role in human lung adenocarcinoma cells and attenuated the apoptotic cascade. Collectively, combined treatment of DMAS and pharmacological autophagy inhibitors could offer an effective therapeutic strategy for lung adenocarcinoma treatment.

Topics: A549 Cells; Adenocarcinoma; Apoptosis; Autophagy; Autophagy-Related Protein 5; Cell Line, Tumor; Cell Survival; Endoplasmic Reticulum Stress; Humans; Lung Neoplasms; Naphthoquinones; RNA Interference; Signal Transduction; Transcription Factor CHOP; Unfolded Protein Response

The naphthopyranones paepalantine and 5-methoxy-3,4-dehydroxanthomegnin isolated from Paepalanthus sp, showed in previous studies antioxidant, anti-inflammatory, antitumour and antimicrobial potential, such as anti-Helicobacter pylori activity. H. pylori infection is one of the main causes of gastric cancer, causing an excessive inflammatory response through the neutrophils and macrophages infiltration, increasing the release of reactive species and thus inducing the production of pro-inflammatory mediators. In the present study, immunomodulatory activity of naphthopyranones in LPS-stimulated macrophages and cytotoxic action in gastric adenocarcinoma cell lines was evaluated. The potential of interaction of these substances in the iNOS binding site was investigated by molecular docking. Cytotoxic activity in gastric adenocarcinoma cells (AGS) was evaluated by the MTT assay. The results evidenced immunomodulatory potential by inhibiting the pro-inflammatory cytokines and nitric oxide produced by LPS-stimulated macrophages. Cytotoxic activity in AGS cell line was also reported. The results indicated that the studied naphthopyranones are viable alternatives in the treatment and prevention of H. pylori infection as well as the diseases related to this infection, especially gastric cancer.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Computer Simulation; Cytokines; Eriocaulaceae; Helicobacter Infections; Helicobacter pylori; Humans; Immunologic Factors; Isocoumarins; Lipopolysaccharides; Macrophages; Mice; Molecular Docking Simulation; Naphthoquinones; Nitric Oxide; Nitric Oxide Synthase Type II; RAW 264.7 Cells; Stomach Neoplasms

Lawsone (LS) a colored napthoquinone compound obtained from the plant Lawsonia inermis L. (Lythraceae) is known for its usefulness of being a precursor for synthesis of some anticancer compounds. Literatures support potent anticancer activity of napthoquinone derivatives in human colon cancer, present study evaluates the effect and mechanism of LS on chemical induced colon cancerous rats and human colon cancer DLD-1 cells, the study was supported by endoscopy, histological and immunohistochemistry analysis. KAD rats were subjected to colon cancer mediated by Azoxymethane (AOM) injections followed Dextran sodium sulfate (DSS) orally in drinking water. After endoscopic confirmation the rats were given LS (200mg/ml) orally for 8 weeks. Presence of aberrant foci, types of tumors and the proliferative effect on tumor lesions was studied by macroscopic, histological and immunohistochemical analysis. To establish the mechanism, human colon DLD-1 cancer cells were exposed to LS and its effect on proliferation were studied. LS reduced aberrant crypt without affecting tumor pathology. Histological study of colon suggested decrease in numbers of adenomas and lesions. Immunohistochemistry confirmed the antiproliferative activity in adenocarcinomas without affecting the cells of normal colon mucosa. Results on human DLD-1 cells showed LS delayed progression of cell cycle by decreasing expression of cyclin B1 as well as cdk1 by inactivating NF-κB without inducing apoptosis. The study concluded role of LS in suppressing cell proliferation of colon tumors. The suppressive activity on DLD-1 cells was not by apoptosis but by decreased NF-κB activity resulting in suppression of expression levels of cyclin B1 and cdk1.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Azo Compounds; Carcinogens; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Dextran Sulfate; Endoscopy; Humans; Intestinal Mucosa; Naphthoquinones; NF-kappa B; Rats; Signal Transduction

Photodynamic therapy (PDT) represents a rapidly developing alternative treatment for various types of cancers. Although considered highly effective, cancer cells can exploit various mechanisms, including the upregulation of apoptosis inhibitors, to overcome the cytotoxic effect of PDT. Survivin, a member of the inhibitor of apoptosis protein family, is known to play a critical role in cancer progression and therapeutic resistance and therefore represents a potential therapeutic target. The aim of this study was to investigate whether YM155, a small molecule inhibitor of survivin expression, can potentiate the cytotoxic effect of hypericin-mediated PDT (HY-PDT). Accordingly, two cell lines resistant to HY-PDT, HT-29 (colorectal adenocarcinoma) and A549 (lung adenocarcinoma), were treated either with HY-PDT alone or in combination with YM155. The efficacy of different treatment regimens was assessed by MTT assay, flow cytometry analysis of metabolic activity, viability, phosphatidylserine externalisation, mitochondrial membrane potential and caspase-3 activity and immunoblotting for the cleavage of poly (ADP-ribose) polymerase (PARP). Here we show for the first time that the repression of survivin expression by YM155 is effective in sensitizing HT-29 and A549 cells to HY-PDT, as measured by the decrease in cell viability and induction of apoptosis. Combined treatment with hypericin and YM155 led to a more severe dissipation of the mitochondrial membrane potential and caused an increase in caspase-3 activation and subsequent PARP cleavage. Our results demonstrate that the repression of survivin expression by YM155 potentially represents a novel alternative strategy to increase the efficacy of HY-PDT in cancer cells that are otherwise weakly responsive or non-responsive to treatment.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Anthracenes; Antineoplastic Agents; Autophagy; Caspase 3; Cell Cycle; Cell Line, Tumor; Cell Survival; Colorectal Neoplasms; Drug Resistance, Neoplasm; Humans; Imidazoles; Inhibitor of Apoptosis Proteins; Lung Neoplasms; Membrane Potential, Mitochondrial; Naphthoquinones; Perylene; Photochemotherapy; Photosensitizing Agents; Survivin

β, β-Dimethylacrylshikonin (DMAS) is an anticancer compound extracted from the roots of Lithospermum erythrorhizon. In the present study, we investigated the effects of DMAS on human lung adenocarcinoma cells in vitro and explored the mechanisms of its anti-cancer action.. Human lung adenocarcinoma A549 cells were tested. Cell viability was assessed using an MTT assay, and cell apoptosis was evaluated with flow cytometry and DAPI staining. The expression of the related proteins was detected using Western blotting. The mitochondrial membrane potential was measured using a JC-1 kit, and subcellular distribution of cytochrome c was analyzed using immunofluorescence staining.. Treatment of A549 cells with DMAS suppressed the cell viability in dose- and time-dependent manners (the IC50 value was 14.22 and 10.61 μmol/L, respectively, at 24 and 48 h). DMAS (7.5, 10, and 15 μmol/L) dose-dependently induced apoptosis, down-regulated cIAP-2 and XIAP expression, and up-regulated Bax and Bak expression in the cells. Furthermore, DMAS resulted in loss of mitochondrial membrane potential and release of cytochrome c in the cells, and activated caspase-9, caspase-8, and caspase-3, and subsequently cleaved PARP, which was abolished by pretreatment with Z-VAD-FMK, a pan-caspase inhibitor. DMAS induced sustained p38 phosphorylation in the cells, while pretreatment with SB203580, a specific p38 inhibitor, blocked DMAS-induced p38 activation and apoptosis.. DMAS inhibits the growth of human lung adenocarcinoma A549 cells in vitro via activation of p38 signaling pathway.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Apoptosis; Cell Line, Tumor; Humans; Lung Neoplasms; MAP Kinase Signaling System; Mitochondria; Naphthoquinones; Signal Transduction

Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4(+)) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 ppm) inhibits tumor development in intact as well as castrated Pten-KO mice. Plumbagin has shown no signs of toxicity at either of these doses. Plumbagin treatment resulted in a decrease expression of PKCε, AKT, Stat3, and COX2 compared with the control mice. Plumbagin treatment also inhibited the expression of vimentin and slug, the markers of epithelial-to-mesenchymal transition (EMT) in prostate tumors. In summary, the results indicate that dietary plumbagin inhibits growth of both primary and castration-resistant prostate cancer (CRPC) in Pten-KO mice, possibly via inhibition of PKCε, Stat3, AKT, and EMT markers (vimentin and slug), which are linked to the induction and progression of prostate cancer.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Biomarkers; Carcinogenesis; Epithelial-Mesenchymal Transition; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Naphthoquinones; Orchiectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Protein Kinase C-epsilon; PTEN Phosphohydrolase; Signal Transduction; STAT3 Transcription Factor

The compound 2-methoxy-1,4-naphthoquinone (MNQ) was previously shown to be cytotoxic against several cancer cell lines, but its mode of action is poorly understood. In this study, we aimed to explore the molecular mechanism of MNQ-induced cytotoxicity of A549 lung adenocarcinoma cells.. The growth inhibition potential of MNQ was analyzed using sulforhodamine B assay, flow cytometry cell cycle analysis and Annexin V apoptosis assay. Oxidative stress was determined using 2',7'-dichlorofluorescein diacetate to measure intracellular reactive oxygen species level and comet assay to measure DNA damage. Western blotting was performed to study the activation of mitogen-activated protein kinase signaling pathways.. MNQ induced apoptosis of A549 cells independent of cell cycle arrest, and is mediated by the JNK and p38 MAPK signaling pathways. Further analysis demonstrated that these signaling pathways were stimulated by oxidative DNA damage caused by increased ROS generation in MNQ-treated A549 cells.. This study is the first to provide an insight into the molecular mechanism of MNQ-induced cytotoxicity of a lung cancer cell, which demonstrates the potential of MNQ as a potential chemotherapeutic drug for lung cancer treatment.

Topics: Adenocarcinoma; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cytotoxins; DNA Damage; Humans; Lung Neoplasms; MAP Kinase Kinase 4; MAP Kinase Signaling System; Naphthoquinones; Neoplasm Proteins; Oxidation-Reduction; Oxidative Stress; p38 Mitogen-Activated Protein Kinases

Hand-foot syndrome (HFS) is the most frequently reported side effect of oral capecitabine therapy. In addition to treatment interruption and dose reduction, supportive treatments can help alleviate symptoms. Although its efficacy has not been proven in clinical studies, certain authors report on the use of prophylactic or therapeutic pyridoxine supplementation for the prevention of minimization to be useful in preventing worsening of HFS but are no substitute for dose modifications.. We report a case of an interesting observation in a patient with pancreatic cancer receiving capecitabine whose HFS was improved with the use of "henna".. Henna has been used for histories as a medicine, preservative, and cosmetic. Our case underlines the basis to further evaluate the anti-inflammatory, antipyretic, and analgesic effects of henna. We encourage other investigators to publish any similar cases or any other herbal or non-drug therapies. HFS is a common side effect of many drugs, including capecitabine, sorafinib and regorafenib. HFS is bothersome for patients even in low grades and impacts quality of life of patients. HFS cannot be prevented and currently the treatments aimed at controlling syndrome are not very effective. Exploring other potential treatment or management options such as henna is of high value.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Capecitabine; Deoxycytidine; Female; Fluorouracil; Hand-Foot Syndrome; Humans; Middle Aged; Naphthoquinones; Pancreatic Neoplasms

β-lapachone, a major component in an ethanol extract of Tabebuia avellanedae bark, is a promising potential therapeutic drug for various tumors, including lung cancer, the leading cause of cancer-related deaths worldwide. In the first part of this study, we found that apoptotic cell death induced in lung cancer cells by high concentrations of β-lapachone was mediated by increased activation of the pro-apoptotic factor JNK and decreased activation of the cell survival/proliferation factors PI3K, AKT, and ERK. In addition, β-lapachone toxicity was positively correlated with the expression and activity of NAD(P)H quinone oxidoreductase 1 (NQO1) in the tumor cells. In the second part, we found that the FDA-approved non-steroidal anti-inflammatory drug sulindac and its metabolites, sulindac sulfide and sulindac sulfone, increased NQO1 expression and activity in the lung adenocarcinoma cell lines CL1-1 and CL1-5, which have lower NQO1 levels and lower sensitivity to β-lapachone treatment than the A549 cell lines, and that inhibition of NQO1 by either dicoumarol treatment or NQO1 siRNA knockdown inhibited this sulindac-induced increase in β-lapachone cytotoxicity. In conclusion, sulindac and its metabolites synergistically increase the anticancer effects of β-lapachone primarily by increasing NQO1 activity and expression, and these two drugs may provide a novel combination therapy for lung cancers.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Cell Line, Tumor; Drug Synergism; Humans; Lung Neoplasms; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Sulindac; Up-Regulation

Shikonin, a small-molecule natural product which inhibits the activity of pyruvate kinase M2 (PKM2), has been studied as an anti-cancer drug candidate in human cancer models. Here, our results demonstrate that shikonin is able to sensitize human breast cancer cells to chemotherapy by paclitaxel (taxol). Human breast adenocarcinoma MBA-MD-231 cells, which have higher levels of PKM2 expression and activity compared with MCF-7 cells, were selected to study further. The concentrations of shikonin and taxol were first selected at which they did not significantly induce cytotoxicity when treated alone, whereas the combination induced apoptosis. Surprisingly, PKM2 activity was decreased by shikonin, but not by the combination treatment. To identify the potential targets of this combination, human phospho-kinase antibody array analysis was performed and results indicated that the combination treatment inhibited the activation of ERK, Akt, and p70S6 kinases, which are known to contribute to breast cancer progression. Finally, how the combination affects breast cancer cell growth in vivo was tested using a xenograft tumor model. The results indicated that shikonin plus taxol prolonged animal survival and reduced tumor size than the vehicle treatment group. In summary, our results suggest that shikonin has a potential as an adjuvant for breast cancer therapy.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Drug Interactions; Drug Therapy, Combination; Female; Heterografts; Humans; Mice; Mice, Nude; Naphthoquinones; Paclitaxel

Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, can exert inhibitory effect on tumor cell growth. However, little has been known concerning the effect of shikonin on lung adenocarcinoma cell and underlying mechanisms. In the present study, we investigated the effect of shikonin on the proliferation, cell cycle arrest, and apoptosis in human lung adenocarcinoma cells. We found that shikonin significantly suppressed the proliferation of lung adenocarcinoma cells compared with control in dose- and time-dependent manner (P < 0.05). In the meantime, our results showed that shikonin markedly increased the proportion of A549 cells at stage G1 as well as induced apoptosis in A549 cells. Furthermore, suppressed CCND1 and elevated caspase3 and caspase7 expression levels at mRNA were found in this study, indicating that shikonin may inhibit the growth of lung adenocarcinoma cell by changing cell cycle and promoting cell apoptosis through the regulation of CCND1, caspase3, and caspase7. Although more studies are needed, this study suggests that shikonin has the potential to be used as an anti-cancer agent in the treatment of lung adenocarcinoma.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents; Apoptosis; Caspases; Cell Line, Tumor; Cell Proliferation; Enzyme Activation; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Naphthoquinones; Resting Phase, Cell Cycle

Salvicine is a pharmacologically active derivative from Chinese medicinal plant Salvia prionitis Hance (Labiatae). It has been reported that salvicine inactivates β1 integrin and inhibits integrin-mediated cell adhesion to fibronectin. Given the emerging correlation between integrins and angiogenesis, we propose that salvicine abolishes cell adhesion and subsequent metastasis by inhibiting angiogenisis.. The anti-angiogenesis activities of salvicine were investigated for the first time.. The cytotoxicity of salvicine on human microvascular endothelial cells (HMECs) and non-small cell lung adenocarcinoma A549 cells were measured at doses between 0.625 and 200 µM. Changes of cell migration were detected with doses of salvicine at 1.25-5 µM, and basement membrane matrigel matrix was used for the assessment of tube formation at concentrations ranging from 0.078 to 1.25 µM. In addition, mRNA expression of basic fibroblast growth factor (bFGF) in A549 cells was studied with the RT-PCR assay.. In vitro studies revealed that the IC50 of salvicine on A549 cells (18.66 µM) was two-fold higher than that of HMECs (7.91 µM). Salvicine (1.25, 2.5 and 5.0 μM) inhibited significantly the endothelial cell migration up to 56, 73 and 82%, respectively. Salvicine decreased capillary-like tube formation of HMECs with high potency. Furthermore, it (30 µM) markedly reduced the mRNA expression of bFGF in A549 cells, while vascular endothelial growth factor (VEGF) mRNA expression remained unchanged.. Our results suggest that salvicine has potent anti-angiogenic activity through the inhibition on the sequential angiogenic cascades: proliferation, migration and tube formation and is associated with influence on the expression of bFGF of tumor cell.

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Endothelium, Vascular; Fibroblast Growth Factor 2; Gene Expression Regulation, Neoplastic; Humans; Inhibitory Concentration 50; Lung Neoplasms; Naphthoquinones; Neovascularization, Pathologic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Salvia

β-Lapachone (β-Lap) is a 1,2-orthonaphthoquinone that selectively induces cell death in human cancer cells through NAD(P)H:quinone oxidoreductase-1 (NQO1). NQO1 is overexpressed in a variety of tumors, as compared to normal adjacent tissue. However, the low solubility and non-specific distribution of β-Lap limit its suitability for clinical assays. We formulated β-Lap in an optimal random methylated-β-cyclodextrin/poloxamer 407 mixture (i.e., β-Lap ternary system) and, using human breast adenocarcinoma MCF-7 cells and immunodeficient mice, performed in vitro and in vivo evaluation of its anti-tumor effects on proliferation, cell cycle, apoptosis, DNA damage, and tumor growth. This ternary system is fluid at room temperature, gels over 29 °C, and provides a significant amount of drug, thus facilitating intratumoral delivery, in situ gelation, and the formation of a depot for time-release. Administration of β-Lap ternary system to MCF-7 cells induces an increase in apoptosis and DNA damage, while producing no changes in cell cycle. Moreover, in a mouse xenograft tumor model, intratumoral injection of the system significantly reduces tumor volume, while increasing apoptosis and DNA damage without visible toxicity to liver or kidney. These anti-tumoral effects and lack of visible toxicity make this system a promising new therapeutic agent for breast cancer treatment.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cyclodextrins; DNA Damage; Drug Delivery Systems; Female; Humans; Mice; Mice, SCID; Naphthoquinones; Poloxamer; Rheology; Temperature; Xenograft Model Antitumor Assays

2-Methoxy-1,4-naphthoquinone (MeONQ) from Impatiens balsamina L. exhibited strong anti-H. pylori activity in our previous study. In this study, we investigated the cytotoxicity of MeONQ against gastric adenocarcinoma (MKN45 cell line) and propose the relevant mechanisms. MeONQ resulted in serious necrosis via superoxide anion catastrophe when the treatment doses were higher than 50μM, whereas apoptosis occurred at low treatment doses (25-50μM) through the caspase-dependent apoptosis pathway. Necrosis is the dominant mode of cell death. MeONQ exhibited high ability to induce gastric adenocarcinoma necrosis, showing good potential as a candidate agent for H. pylori infection related disease therapy.

Topics: Adenocarcinoma; Anti-Bacterial Agents; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Helicobacter pylori; Humans; Impatiens; Molecular Structure; Naphthoquinones; Reactive Oxygen Species

Plumbagin (PL), 5-hydroxy-2-methyl-1,4-naphthoquinone, is a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L. (also known as chitrak). PL has also been found in Juglans regia (English Walnut), Juglans cinerea (whitenut) and Juglans nigra (blacknut). The roots of P. zeylanica have been used in Indian and Chinese systems of medicine for more than 2500 years for the treatment of various types of ailments. We were the first to report that PL inhibits the growth and invasion of hormone refractory prostate cancer (PCa) cells [Aziz,M.H. et al. (2008) Plumbagin, a medicinal plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer. Cancer Res., 68, 9024-9032.]. Now, we present that PL inhibits in vivo PCa development in the transgenic adenocarcinoma of mouse prostate (TRAMP). PL treatment (2 mg/kg body weight i.p. in 0.2 ml phosphate-buffered saline, 5 days a week) to FVB-TRAMP resulted in a significant (P < 0.01) decrease in prostate tumor size and urogenital apparatus weights at 13 and 20 weeks. Histopathological analysis revealed that PL treatment inhibited progression of prostatic intraepithelial neoplasia (PIN) to poorly differentiated carcinoma (PDC). No animal exhibited diffuse tumor formation in PL-treated group at 13 weeks, whereas 75% of the vehicle-treated mice elicited diffuse PIN and large PDC at this stage. At 20 weeks, 25% of the PL-treated animals demonstrated diffuse PIN and 75% developed small PDC, whereas 100% of the vehicle-treated mice showed large PDC. PL treatment inhibited expression of protein kinase C epsilon (PKCε), signal transducers and activators of transcription 3 phosphorylation, proliferating cell nuclear antigen and neuroendocrine markers (synaptophysin and chromogranin-A) in excised prostate tumor tissues. Taken together, these results further suggest PL could be a novel chemopreventive agent against PCa.

Topics: Adenocarcinoma; Animals; Anticarcinogenic Agents; Antigens, Polyomavirus Transforming; Chromogranin A; Disease Models, Animal; Male; Mice; Mice, Transgenic; Naphthoquinones; Phosphorylation; Proliferating Cell Nuclear Antigen; Prostatic Neoplasms; Protein Kinase C-epsilon; STAT3 Transcription Factor; Synaptophysin

A series of mansonone F (MF) derivatives were designed and synthesized. These compounds were found to be strong inhibitors for topoisomerases, with much more significant inhibition for topoisomerase II rather than topoisomerase I. The best inhibitor showed 20 times stronger anti-topoisomerase II activity than a positive control Etoposide. The cytotoxic activity of these MF derivatives was evaluated against human cancer cell lines CNE-2 and Glc-82, which showed that these compounds were potent antitumor agents. The structure-activity relationships (SARs) study revealed that o-quinone group and pyran ring are important for their cytotoxic activity.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antigens, Neoplasm; Antineoplastic Agents; Carcinoma; Cell Line, Tumor; Cell Survival; DNA; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; DNA-Binding Proteins; Drug Screening Assays, Antitumor; Etoposide; Humans; Inhibitory Concentration 50; Lung Neoplasms; Naphthoquinones; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Plasmids; Pyrans; Quinones; Sesquiterpenes; Structure-Activity Relationship; Telomerase; Topoisomerase Inhibitors

Naphtho[1,2-b]furan-4,5-dione (NFD), prepared from 2-hydroxy-1,4-naphthoquinone and chloroacetaldehyde in an efficient one-pot reaction, exhibits an anti-carcinogenic effect. This study was performed to elucidate whether EGFR and PI3K signaling pathways are involved in NFD-induced apoptosis of human lung adenocarcinoma A549 cells.. The effect of NFD on cell viability and apoptosis was measured by the MTT assay and flow cytometry. The phosphorylation levels of EGFR and its regulatory molecules by NFD treatment were studied by immunoblots.. Immunoblot showed that NFD inhibited EGFR phosphorylation and the activation of PI3K/Akt, downstream molecules of EGFR pathway, in A549 cells. The levels of downstream targets of Akt, including phospho-glycogen synthase kinase-3beta (p-GSK-3beta), GSK-3beta, forkhead transcription factor (FKHR), and cyclin D1, were also reduced after NFD treatment. Moreover, inactivation of nuclear factor-kappaB (NFkappaB), modulation of IkappaKalpha/beta and IkappaBalpha, up-regulation of Bad and Bax, and down-regulation of anti-apoptotic proteins including phospho-Bad, Bcl-2, survivin, and XIAP were also found in NFD-treated cells. In addition, NFD treatment disrupted mitochondrial membrane potential (DeltaPsim) and resulted in release of mitochondrial cytochrome c and activation of both caspases-9 and caspase-3.. These findings indicate that EGFR and PI3K/Akt signaling pathways play important roles in NFD-induced apoptosis of A549 cells.

Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Blotting, Western; Caspase 3; Caspase 9; Cell Line, Tumor; Cell Survival; Cytochromes c; Cytosol; ErbB Receptors; Flow Cytometry; Humans; Lung Neoplasms; Membrane Potential, Mitochondrial; Mitochondria; Molecular Structure; Naphthoquinones; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction

A series of new natural tanshinone-like oxoheterocyclic-fused ortho-quinone derivatives were synthesized from readily available benzofuranol and N-substituted dienes via IBX oxidation-cycloaddition-aromatization procedure. The regiospecific Diels-Alder cycloaddition reactions of N-dienes were achieved efficiently with a variety of dienophiles. It is found that the amide moiety in the molecular could be preserved or eliminated by control of the aromatization conditions. Selected oxoheterocyclic-fused ortho-quinones as well as several thioheterocyclic-fused ortho-quinones we obtained before were evaluated for their cytotoxicities on different cancer cell lines and the Structure-Activity Relationship (SAR) was discussed.

Topics: Adenocarcinoma; Antineoplastic Agents; Carcinoma; Cell Line, Tumor; Cell Proliferation; Furans; Humans; Lung Neoplasms; Models, Molecular; Molecular Structure; Naphthoquinones; Nasopharyngeal Neoplasms; Stereoisomerism; Structure-Activity Relationship

The selenoprotein thioredoxin reductase 1 (TrxR1) is currently recognized as a plausible anticancer drug target. Here we analyzed the effects of TrxR1 targeting in the human A549 lung carcinoma cell line, having a very high basal TrxR1 expression. We determined the total cellular TrxR activity to be 271.4 +/- 39.5 nmol min(-1) per milligram of total protein, which by far exceeded the total thioredoxin activity (39.2 +/- 3.5 nmol min(-1) per milligram of total protein). Knocking down TrxR1 by approx 90% using siRNA gave only a slight effect on cell growth, irrespective of concurrent glutathione depletion (> or = 98% decrease), and no increase in cell death or distorted cell cycle phase distributions. This apparent lack of phenotype could probably be explained by Trx functions being maintained by the remaining TrxR1 activity. TrxR1 knockdown nonetheless yielded drug-specific modulation of cytotoxic efficacy in response to various chemotherapeutic agents. No changes in response upon exposure to auranofin or juglone were seen after TrxR1 knockdown, whereas sensitivity to 1-chloro-2,4-dinitrobenzene or menadione became markedly increased. In contrast, a virtually complete resistance to cisplatin using concentrations up to 20 microM appeared upon TrxR1 knockdown. The results suggest that high overexpression of TrxR has an impact not necessarily linked to Trx function that nonetheless modulates drug-specific cytotoxic responses.

Topics: Adenocarcinoma; Apoptosis; Auranofin; Cell Cycle; Cell Growth Processes; Cell Line, Tumor; Cisplatin; Dinitrochlorobenzene; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Naphthoquinones; RNA, Small Interfering; Thioredoxin Reductase 1; Vitamin K 3

Cellular response to chemotherapeutic drugs in the absence of BRCA1 either completely or partially had drawn less attention. The present study evaluated whether there is a differential inhibition of cell growth by selected compounds with respect to BRCA1 status in estrogen receptor (ER)-positive ovarian cancer cells.. The BG1 ovarian cancer cells used in the experiments were antisensely blocked with BRCA1 gene. Growth inhibition and apoptotic induction were analyzed to evaluate the cytotoxic effects. Small interfering RNA (SiRNA) transfection, western blot analysis, RT-PCR analysis and molecular modeling were carried out to analyze the estrogen-dependent action of plumbagin.. Although we found that all the compounds studied induce apoptosis, the induction was in the order of plumbagin > doxorubicin > tamoxifen > cisplatin. Plumbagin can bind to the active site of ER-alpha. Plumbagin, however, induced ER-alpha 46 kDa truncated isoform, which was found abundantly preempted in the cytoplasm compared with a 66-kDa full-length isoform. The truncated isoform is known to inhibit classical ER-alpha signaling pathways. SiRNA-transfected cells for ER-alpha exhibited lower cytotoxicity upon plumbagin treatment than the control-transfected cells.. Taken together, this study indicates that plumbagin has chemotherapeutic potential in BRCA1-mutated/defective ER-positive cancers.

Topics: Actins; Adenocarcinoma; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Biomarkers, Tumor; Blotting, Western; Cell Line, Tumor; Cisplatin; Doxorubicin; Estrogen Receptor alpha; Female; Genes, BRCA1; Humans; Lethal Dose 50; Naphthoquinones; Ovarian Neoplasms; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Signal Transduction; Tamoxifen; Transfection; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases

The cytotoxicity of naphthazarin derivatives isolated from the roots of Onosma arenaria on human cervix adenocarcinoma cells (HeLa) and leukaemia K562 cells, as well on non-malignant peripheral blood mononuclear cells (PBMC) was studied. The results show that beta-hydroxyisovalerylalkannin, acetylalkannin and the pigment fraction exhibited high cytotoxicity in vitro against the tested cell lines, as well the healthy PBMC before or after activation with phytohaemagglutinin.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Boraginaceae; Cell Line, Tumor; Female; Humans; Inhibitory Concentration 50; Leukemia; Leukocytes, Mononuclear; Naphthoquinones; Phytohemagglutinins; Phytotherapy; Plant Roots; Uterine Cervical Neoplasms

A highly sensitive telomerase detection method that involves amplified telomerase analysis and the use of rotating magnetic particles has been developed. Magnetic particles, functionalized with a primer (1) that is recognized by telomerase, are mixed with a nucleotide mixture that includes biotinylated-dUTP, and telomerase-induced elongation of the primers proceeds with simultaneous biotin incorporation. Avidin-Horseradish peroxidase conjugate, coupled to biotin labels, yields the biocatalytic functional particles. Mixing the resulting particles with naphthoquinone-modified magnetic particles enables the optoelectronic detection of telomerase. Attraction of the magnetic particles to an electrode, followed by rotation of the particles, causes the electrocatalytic reduction of O(2) to H(2)O(2) and HRP-catalyzed oxidation of luminol (3); this results in chemilumunescence. The intensity of the emitted light depends on the telomerase content of the sample and the rotation speed of the particles. A minimum number of 10 cancer cells could be detected.

Topics: Adenocarcinoma; Biosensing Techniques; Biotinylation; Carcinoma, Squamous Cell; Cells, Cultured; DNA; HeLa Cells; Horseradish Peroxidase; Humans; Hydrogen Peroxide; Kidney; Luminescent Measurements; Luminol; Lung Neoplasms; Magnetics; Naphthoquinones; Sensitivity and Specificity; Telomerase

The telomere and telomerase have been suggested as targets for anticancer drug discovery. However, the mechanisms by which conventional anticancer drugs affect these targets are currently unclear. The novel topoisomerase II inhibitor, salvicine, suppresses telomerase activity in leukemia HL-60 cells. To further determine whether this activity of salvicine is specific to the hematological tumor and distinct from those of other conventional anticancer agents, we studied its effects on telomere and telomerase in a solid lung carcinoma cell line, A549. Differences in telomerase inhibition and telomere erosion were observed between salvcine and other anticancer agents. All anticancer agents (except adriamycin) induced shortening of the telomere, which was identified independent of replication, but only salvicine inhibited telomerase activity in A549 cells under conditions of high concentration and short-term exposure. At the low concentration and long-term exposure mode, all the tested anticancer agents shortened the telomere and inhibited telomerase activity in the same cell line. Notably, salvicine inhibited telomerase activity more severely than the other agents examined. Moreover, the compound inhibited telomerase activity in A549 cells indirectly in a concentration- and time-dependent manner. Salvicine did not affect the expression of hTERT, hTP1, and hTR mRNA in A549 cells following 4 h of exposure. Okadaic acid protected telomerase from inhibition by salvicine. These results indicate specificity of salvicine and diversity of anticancer agents in the mechanism of interference with telomerase and the telomere system. Our data should be helpful for designing the study in the development of agents acting on telomere and/or telomerase.

Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Cell Division; Cell Line, Tumor; Cell Survival; Enzyme Activation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Naphthoquinones; Telomerase; Telomere; Treatment Outcome

The mechanisms of the antitumor reactions of 2-methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) to human lung adenocarcinoma A549 cells were investigated. A549 cells that received 1.25 microg/ml FNQ3 (IC(50) at 0.35 microg/ml) developed intensive mitochondrial H(2)O(2) production at 1 h. Selective structural mitochondrial swelling, alteration of mitochondrial membrane potential, and cytochrome c and caspase-9 release from the mitochondria occurred 18-24 h later. alpha-Tocopherol inhibited the alteration of both mitochondrial permeability and the leakage of procaspase-9. The caspase-9 was then activated in the cytosol. The expression of Bcl-2 oncoprotein was suppressed by FNQ3, and resulted in apoptosis. The higher dose of 5 microg/ml induced necrosis via severe mitochondrial breakage. These results showed that FNQ3 targets the mitochondria of A549 cells to produce a reactive oxygen species resulting in apoptosis and necrosis.

Topics: Adenocarcinoma; alpha-Tocopherol; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Blotting, Western; Caspase 9; Caspases; Cytochrome c Group; Cytoplasm; DNA Fragmentation; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Flow Cytometry; Genes, bcl-2; Humans; Hydrogen Peroxide; Lung Neoplasms; Membrane Potentials; Microscopy, Confocal; Microscopy, Electron; Mitochondria; Naphthoquinones; Necrosis; Permeability; Tumor Cells, Cultured

In A549 cell culture, significant variability was found in sensitivity to actinomycin D. Using limiting dilution, actinomycin D-susceptible (G4S) and -resistant (D3R) subclones were isolated. G4S cells were also susceptible to protein synthesis inhibitors, a redox cycling quinone, and an electrophile with concomitant activation of caspases 3 and 9. D3R cells were resistant to these agents without caspase activation. Antioxidant profiles revealed that D3R cells had significantly higher glutathione and glutathione reductase activity but markedly lower catalase, glutathione peroxidase, and aldehyde reductase activities than G4S cells. Thus A549 cells contain at least two distinct subpopulations with respect to predisposition to cell death and antioxidant profile. Because sensitivities to agents and the antioxidant profile were inconsistent, mechanisms independent of antioxidants, including the apparent inability to activate caspases in D3R cells, may play an important role. Regardless, the results suggest that antioxidant profiles of asymmetrical cell populations cannot predict sensitivity to oxidants and warn that the use of single subclones is advisable for mechanistic studies using A549 or other unstable cell lines.

Topics: Adenocarcinoma; Aldehydes; Anisomycin; Antioxidants; Apoptosis; Caspases; Cytotoxins; Dactinomycin; Genetic Heterogeneity; Glutathione; Growth Inhibitors; Humans; Hydrogen Peroxide; Lung Neoplasms; Male; Naphthoquinones; Oxidation-Reduction; Oxidative Stress; Protein Synthesis Inhibitors; Superoxide Dismutase; Tumor Cells, Cultured

A wide spectrum of anti-cancer activity of genistein and beta-lapachone in various tumors has been reported in single treatments. In this study the combined effects of genistein and beta-lapachone on the chemosensitivity of LNCaP and PC3 human prostate cancer cells was determined in vitro, using 3-[4,5-dimethylthiazol-2-yl]-2-,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) to study treatment-induced growth inhibition and cytotoxicity and, annexin V-fluoresceine (FI) and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-propidium iodide (PI) assays to determine potential treatment-induced apoptosis and/or necrosis. The results showed: i) that both PC3 and LNCaP are sensitive to single and combination treatments regardless of hormone sensitivity status, ii) that treatment induced dual death pathways (apoptosis and necrosis) in both cell types, iii) that growth inhibition in both cell types correlated positively with cell death via apoptosis at lower drug concentrations and necrosis at higher concentrations, iv) that combination of genistein and beta-lapachone had synergistic inhibitory effects on growth and proliferation in both cell types. The synergistic inhibitory effect was correlated positively with treatment-induced cell death via apoptosis and necrosis. The overall results indicate that combination treatments with beta-lapachone and genistein are more potent in killing both PC3 and LNCaP cancer cells than treatment with either genistein or beta-lapachone alone. beta-lapachone acts at the G1 and S phase checkpoints in the cell cycle, while genistein induces cell cycle arrest at the G2-M stage. The current results are therefore in agreement with the hypothesis that drug combinations that target cell cycles at different critical checkpoints would be more effective in causing cell death. This result provides a rationale for in vivo studies to determine whether beta-lapachone-genistein combination will provide effective chemotherapy for prostate cancer, regardless of the tumor sensitivity to hormone.

Topics: Adenocarcinoma; Antibiotics, Antineoplastic; Apoptosis; Cell Division; Drug Synergism; Drug Therapy, Combination; Estrogens, Non-Steroidal; Humans; Isoflavones; Male; Naphthoquinones; Necrosis; Prostatic Neoplasms; Tumor Cells, Cultured

Salvicine (a novel diterpenoid quinone compound) exhibited a marked antitumor activity on human solid tumor cell lines and BALB/c-nu human carcinoma xenografts in our earlier studies, and it has been chosen as a candidate anticarcinogenic compound in the preclinical research stage. The present study was undertaken in order to observe whether or not the antitumor effect of salvicine is associated with its ability to induce apoptosis. Our results show that salvicine is capable of inhibiting cell proliferation and inducing characteristic changes of apoptosis in both human leukemia K-562 and gastric carcinoma SGC-7901 cells. These effects are dose and time dependent. The results of this study strongly suggest that the antitumor effect of salvicine is associated with its ability to induce apoptosis. Meanwhile, this study also shows that the activity of salvicine against K-562 and SGC-7901 cells is similar with regards to both growth inhibition and apoptosis induction, further indicating that salvicine causes these particular effects on solid tumor cells.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Division; DNA Fragmentation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Naphthoquinones; Stomach Neoplasms; Tumor Cells, Cultured

The shikonin mixture was used for 19 cases of later-stage lung cancer who were not the candidates for operation, radiotherapy and chemotherapy. The clinical observation showed that shikonin mixture could inhibit the growth of lung cancer and improve the immune function of the body. The tumors were reduced over 25% in diameter. The effective rate was 63.3%, remission rate 36.9%, survival rate of one year 47.3%. The intermedium survival period was about 10 months, including adenocarcinoma 10 months, squamous carcinoma 12 months. After treatment the life quality of patients were greatly improved. The patients got better appetite and their body weights were increased. They could manage themselves in daily life. The Karnofsky scores were enhanced by 20. The authors also observed that shikonin mixture could relieve such symptoms as cough, bloody sputum and chest pain caused by lung cancer. The levels of cells and interleukin-2 were increased (P less than 0.001). It had no harmful effects on peripheral blood picture, heart, kidney and liver. Shikonin mixture is safe and effective for later-stage cancer.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents, Phytogenic; Carcinoma, Bronchogenic; Carcinoma, Squamous Cell; Female; Ginsenosides; Humans; Interleukin-2; Killer Cells, Natural; Lung Neoplasms; Male; Middle Aged; Naphthoquinones; Saponins

Topics: Adenocarcinoma; Animals; Anthraquinones; Antineoplastic Agents; Carcinoma; Carcinoma 256, Walker; Cell Line; Leukemia L1210; Mouth Neoplasms; Naphthoquinones; Quinones; Sarcoma 180; Structure-Activity Relationship

Topics: Adenocarcinoma; Alkylating Agents; Animals; Antineoplastic Agents; Cattle; DNA, Neoplasm; Electron Transport; Mice; Mice, Inbred Strains; Mitochondria, Muscle; NADH, NADPH Oxidoreductases; Naphthoquinones; Neoplasms, Experimental; RNA, Neoplasm; Sarcoma 180; Succinate Dehydrogenase

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Carcinoma 256, Walker; Hydrazones; Leukemia L1210; Naphthoquinones; Neoplasms, Experimental; Rats

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cricetinae; Leukocyte Count; Mammary Neoplasms, Experimental; Mice; Naphthoquinones; Neoplasm Transplantation; Neoplasms, Experimental; Sarcoma 180

Topics: Acids; Adenocarcinoma; Alkaloids; Animals; Antineoplastic Agents; Benzopyrans; Body Weight; Depression, Chemical; Mammary Neoplasms, Experimental; Mice; Naphthoquinones; Neoplasm Transplantation; Nuts; Plant Extracts