naphthoquinones and Uterine-Cervical-Neoplasms

Plumbagin is a natural compound known to impede growth of cancerous cells. However, anti-cervical cancer effects of plumbagin and its underlying molecular mechanism still remains elusive. In this study, plumbagin reduced the viability of CaSki cells in a concentration dependent manner and suppressed their colony formation potential. It led to G2/M phase arrest with downregulation of E2F1 and upregulation of p21. Plumbagin reduced mitochondrial membrane potential and concomitantly increased the percentage of apoptotic cells as revealed by annexin V-propidium iodide staining. Real Time PCR and western blotting confirmed that plumbagin induced apoptosis by reducing the expression of pAkt, procaspase 9 and full-length PARP. Furthermore, scratch assay showed that plumbagin suppressed migratory potential of CaSki cells which could be due to the reduced expression and activity of MMP-2 and upregulation of TIMP2. Interestingly, plumbagin also downregulated UHRF1 expression. Transient silencing of UHRF1 like plumbagin, induced G2/M phase arrest, enhanced apoptosis and suppressed metastasis of CaSki cells suggesting the role of UHRF1 in mediating anti-cancer activities of plumbagin. Plumbagin at IC

Topics: Apoptosis; CCAAT-Enhancer-Binding Proteins; Cell Line, Tumor; Cell Proliferation; Female; Humans; Matrix Metalloproteinase 2; Naphthoquinones; Proto-Oncogene Proteins c-akt; Ubiquitin-Protein Ligases; Uterine Cervical Neoplasms

To observe the expression of c-Myc protein in cervical cancer HeLa cells and explore the effect of juglone on the proliferation and apoptosis of HeLa cells by affecting c-Myc ubiquitination.. HeLa cells treated with different concentrations (0, 10, 20, or 50 μmol/L) of juglone or with 20 μmol/L juglone for different time lengths were examined for expression of c-Myc protein with Western blotting. The half-life of c-Myc protein was determined using cycloheximide (CHX) and c-Myc protein degradation was detected using coimmunoprecipitation. We also assessed the effects of 20 μmol/L juglone combined with 0, 1.0 or 2.0 μmol/L MG132 (a proteasome inhibitor) on c-Myc expression. The effects of 20 μmol/L juglone on the proliferation and apoptosis of HeLa cells with RNA interference-mediated knockdown of c-Myc were evaluated with MTT assay and flow cytometry.. Treatment with juglone significantly lowered c-Myc protein expression in HeLa cells in a concentration-and time-dependent manner (. Juglone inhibits proliferation and promotes apoptosis of HeLa cells by affecting the ubiquitination of c-Myc protein.

Topics: Apoptosis; Cell Proliferation; Female; HeLa Cells; Humans; Naphthoquinones; Ubiquitination; Uterine Cervical Neoplasms

Hyaluronic acid (HA)-CD44 pathway showed association with several malignancies. The natural polyphenols Plumbagin, Pongapin and Karanjin showed anti-cancer activities in different tumors including cervical carcinoma. To understand their mechanism of anti-cancer activity, the effect of the compounds on HA-CD44 pathway was analyzed in cervical cancer cell line HeLa. The mRNA expression of three different isoforms of CD44 i.e., CD44s, CD44v3, and CD44v6, was differentially downregulated by the compounds. This was validated by Western blot and immunocytochemical analysis of CD44s.The low molecular weight HA (LMW-HA) showed growth promoting activity in HeLa at low concentration, whereas high molecular weight HA (HMW-HA) had no such effect. The compounds could preferentially downregulate the LMW-HA level in HeLa, as evident in the cell as well as in the cell-free conditioned medium. Concentration-dependent upregulation of HA synthase-2 (HAS2) was seen in the cell by the compounds, whereas differential downregulation of hyalurinidases 1-4 (HYAL 1-4), predominantly HYAL1, were seen. The compounds could also downregulate the downstream target of the pathway p-AKT (T-308) in concentration-dependent manner. Thus, the compounds could attenuate the HA-CD44 pathway in HeLa cell to restrict the tumor growth.

Topics: Benzopyrans; Down-Regulation; Female; Flavones; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Hyaluronan Receptors; Hyaluronic Acid; Naphthoquinones; Neoplasm Proteins; Signal Transduction; Uterine Cervical Neoplasms

Shikonin, the main ingredient of. MTT, wound-healing, transwell assays and flow cytometry experiments were used to measure cell growth, migration, invasion, and cell cycle analysis. Western blot was used to examine protein levels of Snail, Vimentin and E-cadherin. The expression level of miR-183-5p was measured via qRT-PCR. The E-cadherin promoter activity was detected via Secrete-PairTM Dual Luminescence Assay Kit. The transient transfection experiments were used for silencing of E-cadherin and overexpression of Snail genes. Tumor xenograft and bioluminescent imaging experiments were carried out to confirm the in vitro findings.. We showed that shikonin inhibited cell viability, migration and invasion, and induced cell cycle arrest in a dose-dependent manner in cervical cancer Hela and C33a cells. Mechanistically, we found that shikonin increased miR-183-5p expression and inhibited expression of transcription factor Snail protein. The mimics of miR-183-5p reduced, while the inhibitors of miR-183-5p reversed shikonin-inhibited Snail protein expression. In addition, shikonin decreased Vimentin, increased E-cadherin protein expressions and E-cadherin promoter activity, the latter was reversed in cells transfected with exogenous Snail overexpression vectors. Moreover, silencing of E-cadherin significantly abolished shikonin-inhibited cervical cancer cell growth. Similar findings were also observed in vivo using one xenograft mouse model.. Our results show that shikonin inhibits EMT through inhibition of Snail and stimulation of miR-183-5p expressions, which resulted in induction of E-cadherin expression. Thus, blockade of EMT could be a novel mechanism underlying the anti-cervical cancer effects of shikonin.

Topics: Animals; Antigens, CD; Antineoplastic Agents, Phytogenic; Cadherins; Cell Line, Tumor; Dose-Response Relationship, Drug; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Lithospermum; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Naphthoquinones; Snail Family Transcription Factors; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays

We previously showed that microwave assisted synthesis is the best method for the synthesis of naphthoquinone amino acid and chloride-naphthoquinone amino acid derivatives by a complete evaluation of reaction conditions such as stoichiometry, bases, and pH influence. Following the same strategy, we synthesized chloride and non-chloride tyrosine, valine, and tryptophan-naphthoquinones achieving 85-95%, 80-92%, and 91-95% yields, respectively. The cyclic voltammetry profiles showed that both series of naphthoquinone amino acid derivatives mainly display one redox reaction process. Overall, chloride naphthoquinone amino acid derivatives exhibited redox potential values (E

Topics: Antineoplastic Agents; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Chlorides; Drug Design; Drug Screening Assays, Antitumor; Female; HaCaT Cells; Humans; Inhibitory Concentration 50; Microwaves; Naphthoquinones; Oxidation-Reduction; Papillomavirus Infections; Tryptophan; Tyrosine; Uterine Cervical Neoplasms; Valine

Human papillomaviruses (HPVs), for instance, HPV 16 and HPV 18, are concerned associated with cervical cancer. Thus, it is essential to suppress HPVs-in HPV-positive cervical cancer for treating cervical cancer. The purpose of this study was to explore the proposed molecular mechanisms, which that underlies the antintumor potential of juglone to treat of HPV-positive on cervical cancer cells. The results showed that juglone suppressed HPV-positive cell growth in a dose- and time-dependent way. In addition, cell invasion and metastasis were also inhibited by juglone. Nevertheless, when pin 1 was knocked down in HPV-positive cells, cell proliferation, invasion and metastasis were reduced. This study was designed to acquire an understanding of the mechanism of invasion and metastasis in HPV-positive cells suppressed by juglone. It provides evidence of the advantageous use of juglone in the future.

Topics: Cell Line, Tumor; Cell Proliferation; Female; HeLa Cells; Humans; Naphthoquinones; Neoplasm Invasiveness; Neoplasm Metastasis; Papillomaviridae; Papillomavirus Infections; Uterine Cervical Neoplasms

We performed an extensive analysis about the reaction conditions of the 1,4-Michael addition of amino acids to 1,4-naphthoquinone and substitution to 2,3-dichloronaphthoquinone, and a complete evaluation of stoichiometry, use of different bases, and the pH influence was performed. We were able to show that microwave-assisted synthesis is the best method for the synthesis of naphthoquinone-amino acid and chloride-naphthoquinone-amino acid derivatives with 79-91% and 78-91% yields, respectively. The cyclic voltammetry profiles showed that both series of naphthoquinone-amino acid derivatives mainly display one quasi-reversible redox reaction process. Interestingly, it was shown that naphthoquinone derivatives possess a selective antitumorigenic activity against cervix cancer cell lines and chloride-naphthoquinone-amino acid derivatives against breast cancer cell lines. Furthermore, the newly synthetized compounds with asparagine-naphthoquinones (

Topics: Amino Acids; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Female; Humans; Naphthoquinones; Uterine Cervical Neoplasms

Human papillomaviruses (HPVs), such as HPV 16 and HPV 18 are related to cervical cancer. Therefore, it is important to inhibit HPV-positive cervical cancer for treating cervical cancer. This study is aiming at investigating the proposed molecular mechanism, which underlies the antineoplastic potential of the aqueous extract of juglone of HPV-positive cervical cancer cells. According to the results, it is showed that, juglone prohibited HPV positive cervical cancer cells' growth through dose-dependent way. Nevertheless, when pin 1 was knocked down, the proliferation inhibition reduced. The detection of apoptosis and cell cycle also illustrated that juglone influenced HPV positive cells. Western blot expressed the influence mechanism that it affected the B-cell lymphoma 2 (Bcl-2) family and later activated the Caspase-depended apoptosis way. It is contributable for this study to understand the mechanism of inhibiting HPV positive cells by juglone and it also provides an effective strategy for the application of it in the future.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Cytochromes c; Female; Gene Expression Regulation; Human papillomavirus 16; Human papillomavirus 18; Humans; Mitochondria; Naphthoquinones; Up-Regulation; Uterine Cervical Neoplasms

External beam radiotherapy increases the risk of Candida vaginitis in cervical cancer patients, which brings a lot of insufferable influence to their life. Here, we explored the efficacy of alkannin in the treatment of Candida vaginitis after external beam radiotherapy. We exploit thermosensitive hydrogel-mediated alkannin as the topical formulation in a rat model established in our work. Periodic acid-Schiff of vaginas indicated little Candida albicans adhered to the vaginal tissue in treatment group. Additionally, hematoxylin and eosin stain revealed that inflammatory response of high dose alkannin was reduced. Above all, the animal model was first established in our work for the clinical desire. Our results suggested the promising application of alkannin for the disease with satisfying fungicidal activity and anti-inflammatory activity.

Topics: Administration, Topical; Animals; Anti-Infective Agents, Local; Candida albicans; Candidiasis, Vulvovaginal; Disease Models, Animal; Drug Carriers; Female; Hydrogels; Naphthoquinones; Radiotherapy; Rats; Treatment Outcome; Uterine Cervical Neoplasms

In current study, a series of shikonin derivatives were synthesized and its anticancer activity was evaluated. As a result, PMMB232 showed the best antiproliferation activity with an IC

Topics: Antineoplastic Agents; Apoptosis; Carboxylic Acids; Coumarins; Drug Evaluation, Preclinical; Female; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Molecular Docking Simulation; Naphthoquinones; Uterine Cervical Neoplasms

Cervical cancer is the third most common cancer in women worldwide. In the present study, global microRNA profiling for 79 cervical cancer patient samples led to the identification of miR-218 down-regulation in cervical cancer tissues compared to normal cervical tissues. Lower miR-218 expression was associated significantly with worse overall survival (OS), disease-free survival (DFS), and pelvic/aortic lymph node recurrence. In vitro, miR-218 over-expression decreased clonogenicity, migration, and invasion. Survivin (BIRC5) was subsequently identified as an important cervical cancer target of miR-218 using in silico prediction, mRNA profiling, and quantitative real-time PCR (qRT-PCR). Concordant with miR-218 over-expression, survivin knockdown by siRNA decreased clonogenicity, migration, and invasion. YM155, a small molecule survivin inhibitor, significantly suppressed tumor growth and lymph node metastasis in vivo. Our findings demonstrate that the miR-218~survivin axis inhibits cervical cancer progression by regulating clonogenicity, migration, and invasion, and suggest that the inhibition of survivin could be a potential therapeutic strategy to improve outcome in this disease.

Topics: 3' Untranslated Regions; Animals; Blotting, Western; Cell Line, Tumor; Cell Movement; Cell Survival; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Imidazoles; Inhibitor of Apoptosis Proteins; Kaplan-Meier Estimate; Lymphatic Metastasis; Mice, SCID; MicroRNAs; Middle Aged; Naphthoquinones; Neoplasm Invasiveness; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Survivin; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays

To explore the effect of juglone on proliferation and apoptosis of human cervical squamous cancer SiHa cells.. Cultured SiHa cells in the exponential growth phase were grouped into blank control group and 10, 20, 50, 80 and 100 μmol/L juglone treatment groups. Methyl thiazolyl tetrazolium (MTT) assay was adopted to observe the inhibitory effect of juglone on the proliferation of SiHa cells, and then 50% inhibitory concentration (IC50) was calculated through formula. Annexin V-FITC/PI double staining and flow cytometry were used to detect the effect of 20 μmol/L juglone on SiHa cell apoptosis. Western blot was applied to determine the expressions of Bcl-2 and Bax.. MTT assay showed that, compared with the control group, treatment groups all showed significant inhibitory effects on SiHa cell growth, and IC50 was 20.4 μmol/L. Flow cytometry demonstrated that early apoptosis rate of SiHa cells in the control group was (2.46 ± 0.37)%, and after treatment with 20 μmol/L Juglone for 12 hours, the apoptosis rate was raised to (18.47 ± 2.26)%; Western blot analysis showed that the expression of Bcl-2 decreased while the expression of Bax increased significantly in SiHa cells treated with 20 μmol/L juglone.. Juglone could significantly inhibit the proliferation and induce the apoptosis of SiHa cells.

Topics: Apoptosis; bcl-2-Associated X Protein; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Drugs, Chinese Herbal; Female; Humans; Naphthoquinones; Uterine Cervical Neoplasms

A series of ferrocene and (arene)ruthenium(II) complexes attached to the naturally occurring anticancer naphthoquinones plumbagin and juglone was tested for efficacy against various cancer cell lines and for alterations in the mode of action. The plumbagin ferrocene and (p-cymene)Ru(II) conjugates 1c and 2a overcame the multi-drug drug resistance of KB-V1/Vbl cervix carcinoma cells and showed IC50 (72 h) values around 1 μM in growth inhibition assays using 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT). They were further investigated for their influence on the cell cycle of KB-V1/Vbl and HCT-116 colon carcinoma cells, on the generation of reactive oxygen species (ROS) by the latter cell line, for their substrate character for the P-glycoprotein drug eflux pump via the calcein-AM efflux assays, and for DNA affinity by the electrophoretic mobility shift assay (EMSA). The derivatives 1c and 2a increased the number of dead cancer cells (sub-G0/G1 fraction) in a dose- and time-dependent manner. ROS levels were significantly increased upon treatment with 1c and 2a. These compounds also showed a greater affinity to linear DNA than plumbagin. While plumbagin did not affect calcein-AM transport by P-glycoprotein the derivatives 1c and 2a exhibited a 50% or 80% inhibition of the P-glycoprotein-mediated calcein-AM efflux relative to the clinically established sensitizer verapamil.

Topics: Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B; Cell Cycle; Cell Line, Tumor; Colonic Neoplasms; Coordination Complexes; Cymenes; DNA; Female; Ferrous Compounds; Humans; Metallocenes; Monoterpenes; Naphthoquinones; Ruthenium; Uterine Cervical Neoplasms

To explore the effects of Juglone on proliferation and apoptosis of human cervical cancer Caski cells, and to further study the related mechanism of cell apoptosis.. Cultured Caski cells were incubated with 20, 40, 60, 80 and 100 μmol/L juglone for 24 h. The proliferation of Caski cells was detected by methyl thiazolyl tetrazolium (MTT) assay. The cell apoptosis were detected by transmission electron microscope. The expression of Bcl-2 and Bax were detected by Western blot.. MTT results showed that in different doses of juglone groups, the Caski cell growth was greatly inhibited (P < 0.05, P < 0.01) and showed dose dependent when compared with control group except 20 μmol/L. The IC50 of juglone was 42.4 μmol/L. After treatment on Caski cells with 40 μmol/L juglone, typical apoptosis characteristics was observed by transmission electronmicro scope. The expression of Bcl-2 was decreased while the expression of Bax was increased significantly when compared with control group (P < 0.05).. Juglone significantly inhibits the proliferation and induces the apoptosis of Caski cells in vitro.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Cell Cycle; Cell Proliferation; Female; Humans; Microscopy, Electron, Transmission; Naphthoquinones; Uterine Cervical Neoplasms

Benjakul [BEN], a Thai Traditional medicine preparation, is composed of five plants: Piper chaba fruit [PC], Piper sarmentosum root [PS], Piper interruptum stem [PI], Plumbago indica root [PL] and Zingiber officinale rhizome [ZO]. From selective interviews of folk doctors in Southern Thailand, it was found that Benjakul has been used for cancer patients.. To investigate cytotoxicity activity of Benjakul preparation [BEN] and its ingredients against three human cancer cell lines, large lung carcinoma cell line (COR-L23), cervical cancer cell line (Hela) liver cancer cell line (HepG2) as compared with normal lungfibroblast cell (MRC-5) by using SRB assay.. The extraction as imitated the method used by folk doctors was done by maceration in ethanol and boiling in water Bioassay guided isolation was used isolated cytotoxic compound.. The ethanolic extracts of PL, ZO, PC, PS, BEN and PS showed specific activity against lung cancer cell (IC50 = 3.4, 7.9, 15.8, 18.4, 19.8 and 32.91 microg/ml) but all the water extracts had no cytotoxic activity. Three active ingredients [6-gingerol, plumbagin and piperine as 0.54, 4.18 and 7.48% w/w yield of crude extract respectively] were isolated from the ethanolic extract of BEN and they also showed cytotoxic activity with plumbagin showing the highest cytotoxic activity against COR-L23, HepG2, Hela and MRC-5 (IC50 = 2.55, 2.61, 4.16 and 11.54 microM respectively).. These data results may support the Thai traditional doctors who are using Benjakul to treat cancer patients and three of its constituents (6-gingerol, plumbagin and piperine) are suggested to be used as biomarkers for standardization of this preparation.

Topics: Alkaloids; Benzodioxoles; Catechols; Cell Line, Tumor; Fatty Alcohols; Female; Humans; Liver Neoplasms; Lung Neoplasms; Medicine, East Asian Traditional; Naphthoquinones; Phytotherapy; Piper; Piperidines; Plant Extracts; Plants, Medicinal; Plumbaginaceae; Polyunsaturated Alkamides; Thailand; Uterine Cervical Neoplasms; Zingiber officinale

Induction of apoptosis in tumor cells has become the major focus of anti-tumor therapeutics development. Juglone, a major chemical constituent of Juglans mandshurica Maxim, possesses several bioactivities, including anti-tumor. In the present study, HeLa cells were incubated with juglone at various concentrations. The proliferation inhibition of juglone on HeLa cells was tested by the MTT assay. Occurrence of apoptosis was detected by Hoechst 33258 staining, flow cytometry, and transmission electron microscopy. The expression of apoptotic-related proteins was examined by Western blot. The results showed that juglone inhibits the growth of HeLa cells in dose-dependent manner. Topical morphological changes of apoptotic body formation after juglone treatment were observed. The percentages of early apoptosis of Annexin V-FITC were 5.23%, 7.95%, 10.69%, and 20.92% with the concentrations of juglone (12.5, 25, 50, and 100 µmol/L), respectively. After cells were treated with juglone at the different dose for 24 h, the expression of Bcl-2 was significantly down-regulated and the expression of Bax was significantly up-regulated compared with the control. These events paralleled with activation of caspase-9, -8, -3, and PARP cleavage. The results suggest that juglone may be effective for the treatment of HeLa cells.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Blotting, Western; Carcinoma; Caspases; Cell Proliferation; Down-Regulation; Enzyme Activation; Female; HeLa Cells; Humans; Microscopy, Electron, Transmission; Naphthoquinones; Neoplasm Proteins; Osmolar Concentration; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Proteolysis; Up-Regulation; Uterine Cervical Neoplasms

Rhinacanthone, a main bioactive naphthoquinone, isolated from roots of Rhinacanthus nasutus KURZ, (family Acanthaceae), a Thai traditional medicine, has been reported to possess anticancer effects, although the anticancer mechanism is still unclear. Therefore, we investigated the effects of rhinacanthone on cell proliferation, cell cycle progression and apoptosis induction in human cervical carcinoma (HeLa) cells. beta-Lapachone, an anticancer drug having a chemical structure related to rhinacanthone, was used as a positive control. The results demonstrated that rhinacanthone inhibited proliferation of HeLa cells in a dose-dependent manner and had greater efficacy than that of beta-lapachone: IC(50) values of the compound ranged from 1.2+/-0.1 to 5.5+/-0.86 muM for 2-24 h time periods. Rhinacanthone-treated HeLa cells displayed several apoptotic features as evidenced by the appearance of chromatin condensation, internucleosomal DNA fragmentation, increase in the proportion of sub G(1) apoptotic cells, and externalization of annexin-V. The apoptotic processes by the treatment with rhinacanthone involved in a marked increase in the level of pro-apoptotic protein Bax and decrease in the levels of anti-apoptotic proteins Bcl-2 and survivin as well as subsequent activation of caspase-9 and caspase-3. Moreover, rhinacanthone increased the expression of apoptosis-inducing factor (AIF) which would translocate from mitochondria to nucleus through cytosol, and induce apoptosis through caspase independent signaling pathway. Taken together, our findings for the first time demonstrate that rhinacanthone-induced apoptosis in HeLa cells is mediated primarily through the mitochondria-dependent signaling pathway, suggesting that it may be a promising agent for the treatment of human cervical cancer.

Topics: Acanthaceae; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Benzopyrans; Blotting, Western; Cell Cycle; Cell Proliferation; DNA Fragmentation; Female; HeLa Cells; Humans; Naphthoquinones; Plant Roots; Reverse Transcriptase Polymerase Chain Reaction; Uterine Cervical Neoplasms

Radiotherapy is the primary line of cancer treatment for cervical cancer and is known to induce cell death in tumors. Radiotherapy is however limited by the total dose that can be given without damaging normal tissue. Plumbagin, a naturally occurring naphthaquinone, has been reported to have free radical producing properties. Hence we hypothesized that plumbagin could also have properties that could modify effects of radiation on cervical cancer cells. Radiation in combination with plumbagin may thus have treatment augmenting effects. Results from our studies have shown that a lower dose of radiation in combination with plumbagin could induce apoptosis more effectively compared to a higher dose of radiation alone. Plumbagin in combination with 2 Gy of radiation was very effective in inducing apoptosis, when compared to a higher radiation dose of 10 Gy alone. This combination also showed a fivefold increase in the activation of caspase 3 in C33A cells. Activation of effector caspases confirms that the induction of apoptosis by irradiation and plumbagin involves caspase-dependent pathways. Expression of apoptotic regulatory molecules Bcl-2, Bax and Survivin was also modulated by plumbagin in combination with radiation. In summary, this study shows that a combination of plumbagin and radiation augmented cell growth inhibition compared to higher radiation dose alone, thus indicating that plumbagin may be a potential radiosensitizer acting through the induction of apoptosis.

Topics: Apoptosis; Breast; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Female; Gamma Rays; HeLa Cells; Humans; Membrane Potentials; Mitochondrial Membranes; Naphthoquinones; Radiation-Sensitizing Agents; Uterine Cervical Neoplasms

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

There is an emerging evidence that plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone) may have potential as a chemotherapeutic agent. However, the growth inhibitory mechanisms of plumbagin have remained unexplored. The aim of the study was to determine whether plumbagin-induced cell death in human cervical cancer cell line, ME-180, exhibited biochemical characteristics of apoptosis and to check whether N-acetyl-l-cysteine (NAC), which is a free radical scavenger, can reverse the cytotoxic effects of plumbagin. It can be concluded from the results that plumbagin inhibits the growth of ME-180 cells in a concentration and time-dependent manner. The cytotoxic effect of plumbagin induced cell death is through the generation of reactive oxygen species (ROS) and subsequent induction of apoptosis as demonstrated by the present data. Treatment of cells with plumbagin caused loss of mitochondrial membrane potential (DeltaPsi(m)), and morphological changes characteristic of apoptosis, such as the translocation of phosphatidyl serine, nuclear condensation, and DNA fragmentation. Moreover, plumbagin-induced apoptosis involved release of mitochondrial cytochrome c and apoptosis inducing factor (AIF), thus activation of caspase-dependent and -independent pathways, as shown by the plumbagin-mediated activation of caspase-3 and -9. Our results also show that pretreatment of ME-180 cells with NAC blocks plumbagin-induced loss of DeltaPsi(m) and subsequent release of cytochrome c, AIF, and caspase-9 and -3 activation, thus inhibiting the apoptotic ability of plumbagin.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Caspases; Cell Nucleus; Cytochromes c; Dose-Response Relationship, Drug; Female; Humans; Mitochondria; Naphthoquinones; Phosphatidylserines; Reactive Oxygen Species; Time Factors; Uterine Cervical Neoplasms

2-Methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) has been reported to be more cytotoxic to human malignant tumor cell lines than are the corresponding normal epithelial cells. Therefore, we examined the dose response of FNQ3 against human cervical cancer HeLa cells in culture. When 1.25 mg/ml FNQ3 was applied, apoptosis was induced, as determined by an immunohistochemical staining of fragmented genome DNA and cell profiles. Significant inhibition of Bcl-2 oncogene protein expression by the same concentration of FNQ3 also was demonstrated by an immunohistochemical staining method to visualize the expressed cells and Western blot in polyacrylamide gel electrophoresis. Flow-cytometric spectra showed S-phase arrest in cell cycles and the appearance of sub-G1 phase consistent with apoptosis. On the other hand, concentrations of 5 microg/ml or more of FNQ3 induced necrosis. These results show that FNQ3 may act as an antitumor agent to induce apoptosis by affecting Bcl-2 expression and cell cycles, or necrosis as the result of primary mitochondrial injuries.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Blotting, Western; Cell Cycle; Cervix Uteri; DNA; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Epithelial Cells; Female; Flow Cytometry; HeLa Cells; Humans; Immunohistochemistry; Mitochondria; Naphthoquinones; Necrosis; Proto-Oncogene Proteins c-bcl-2; S Phase; Time Factors; Uterine Cervical Neoplasms