ginsenoside-m1 and Lung-Neoplasms

Ginsenoside CK is the main metabolite of protopanaxadiol saponins in intestinal bacteria. Previous studies have shown that ginsenoside CK can affect many aspects of tumor development through a variety of mechanisms. However, few studies have reported the antimetastatic effects of ginsenoside CK in non-small-cell lung cancer (NSCLC). In this study, we explored the effect of ginsenoside CK on epithelial-mesenchymal transition (EMT) induced by TGF-

Topics: A549 Cells; Animals; Cadherins; Cell Line, Tumor; Cell Movement; Down-Regulation; Epithelial-Mesenchymal Transition; Ginsenosides; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Sirtuin 1; Transforming Growth Factor beta; Up-Regulation; Vimentin

Compound K [C-K; 20-

Topics: A549 Cells; AMP-Activated Protein Kinases; Antineoplastic Agents; Apoptosis; Autophagy; Carcinoma, Non-Small-Cell Lung; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Ginsenosides; Humans; JNK Mitogen-Activated Protein Kinases; Lung Neoplasms; Molecular Conformation; Structure-Activity Relationship; TOR Serine-Threonine Kinases

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. Compound K, an active metabolite of ginsenosides, is reported to exhibit anti-cancer property in various types of human malignancies. The present study investigated the role of compound K on glucose metabolism in NSCLC cells and its underlying mechanism. Our study found that compound K dose-dependently inhibited the cell viability of NSCLC cells. Moreover, administration with compound K decreased glucose uptake and lactate secretion under normoxic and hypoxic conditions. Consistently, the expression of key enzymes (HK II, PDK1 and LDHA) involved in glucose metabolism were inhibited in compound K-treated tumor cells. In addition, compound K inhibited the expression of HIF-1α and its downstream gene GLUT1. On the contrary, overexpression of HIF-1α elevated metabolic reactions and partly attenuated the inhibitory role of compound K on NSCLC cell growth. These results demonstrate that compound K suppresses NSCLC cell growth via HIF-1α mediated metabolic alteration, contributing to novel anticancer therapy by targeting glucose metabolism.

Topics: Cell Death; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Ginsenosides; Glucose; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lung Neoplasms

Ginsenoside compound K (CK) has effects on cell-cycle regulation, tumor growth inhibition, and apoptosis induction. However, it has limited applications in clinical settings because of its low solubility and poor absorption.. To overcome these limitations, we aimed to develop a mixed micellar system composed of phosphatidylcholine (PC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol 2000 (DSPE PEG 2000; DP). CK encapsulated in PC/DP mixed micelles had enhanced solubility, permeability, and retention effects.. Compared to free CK, the CK PC/DP micellar system exhibited improved anticancer effects in vitro, including cell-cycle arrest, apoptosis, and anti-invasion in human lung carcinoma A549 cells. The significant proapoptotic effect was reflected by increased chromosomal condensation, annexin V/propidium iodide staining, and related protein expression. In vitro cellular uptake and optical mouse imaging in vivo suggested that the improved antitumor effect was caused primarily by enhanced uptake and tumor targeting. Furthermore, an in vivo antitumor efficacy study indicated that the CK mixed micelles significantly inhibited tumor growth, thereby decreasing tumor volume at the end of the experiment as compared with that in the control mice. Histological analysis confirmed the antitumor effect with low toxicity.. The PC/DP micellar system was an effective drug delivery system for CK in tumor therapy.

Topics: A549 Cells; Animals; Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; Drug Delivery Systems; Ginsenosides; Humans; Lung Neoplasms; Male; Mice, Nude; Micelles; Optical Imaging; Particle Size; Phosphatidylcholines; Phosphatidylethanolamines; Polyethylene Glycols; Solubility; Tumor Burden; Wound Healing

Combinations of natural products with low toxicities using tumor-targeting carriers may improve cancer treatment. The combined parthenolide and ginsenoside compound K (CK) within tLyp-1 liposomes, with the aim of improving the efficacy of lung cancer treatment.. In vitro studies in A549 human pulmonary adenocarcinoma cells demonstrated that parthenolide/CK tLyp-1 liposomes increased reactive oxygen species levels and induced mitochondrial apoptosis. It enters into cells via receptor-mediated uptake and micropinocytosis, followed by endosomal/lysosomal escape. In vivo studies illustrated that it produced a greater antitumor effect than combined administration of these compounds, with minimal toxicity.. The findings of this study indicated that combined application of natural products in nanocarriers could offer attractive therapeutic options.

Topics: A549 Cells; Animals; Apoptosis; Delayed-Action Preparations; Ginsenosides; Humans; Liposomes; Lung Neoplasms; Mice; Mice, Nude; Mitochondria; Reactive Oxygen Species; Sesquiterpenes; Xenograft Model Antitumor Assays

The roles of ginsenoside compound K (CK) in inhibiting tumor have been widely recognized in recent years. However, low water solubility and significant P-gp efflux have restricted its application. In this study, CK ascorbyl palmitate (AP)/d-α-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS) mixed micelles were prepared as a delivery system to increase the absorption and targeted antitumor effect of CK. Consequently, the solubility of CK increased from 35.2±4.3 to 1,463.2±153.3 μg/mL. Furthermore, in an in vitro A549 cell model, CK AP/TPGS mixed micelles significantly inhibited cell growth, induced G0/G1 phase cell cycle arrest, induced cell apoptosis, and inhibited cell migration compared to free CK, all indicating that the developed micellar delivery system could increase the antitumor effect of CK in vitro. Both in vitro cellular fluorescence uptake and in vivo near-infrared imaging studies indicated that AP/TPGS mixed micelles can promote cellular uptake and enhance tumor targeting. Moreover, studies in the A549 lung cancer xenograft mouse model showed that CK AP/TPGS mixed micelles are an efficient tumor-targeted drug delivery system with an effective antitumor effect. Western blot analysis further confirmed that the marked antitumor effect in vivo could likely be due to apoptosis promotion and P-gp efflux inhibition. Therefore, these findings suggest that the AP/TPGS mixed micellar delivery system could be an efficient delivery strategy for enhanced tumor targeting and antitumor effects.

Topics: A549 Cells; Animals; Apoptosis; Ascorbic Acid; Cell Cycle; Cell Movement; Drug Delivery Systems; Endocytosis; Ginsenosides; Humans; In Situ Nick-End Labeling; Lung Neoplasms; Mice, Nude; Micelles; Succinates; Tumor Burden; Vitamin E

Pretreatment of NCI-H460 human lung cancer cells with compound K produced by intestinal bacteria enhances gamma-ray radiation-induced cell death. Increases in apoptosis induced by combined treatment are made apparent in the observation of nuclear fragmentation, loss of mitochondrial membrane potential (Deltapsi), and activation of caspase 3. Apoptosis induced by compound K and gamma-ray radiation is associated with reactive oxygen species (ROS) generation. Furthermore, compound K, in combination with gamma-ray radiation, has an enhanced effect in the regression of NCI-H460 tumor xenografts of nude mice. These results suggest that compound K has possible application for cancer therapy when used in combination with gamma-ray radiation.

Topics: Animals; Apoptosis; Cell Line, Tumor; Combined Modality Therapy; Gamma Rays; Ginsenosides; Humans; Lung Neoplasms; Membrane Potential, Mitochondrial; Mice; Mice, Nude; Panax; Saponins

SC-514, an inhibitor of IkappaB kinase beta (IKKbeta), blocked the TNF-alpha-induced activation of nuclear factor-kappaB (NF-kappaB) as well as the TNF-alpha-promoted metastasis of murine colon adenocarcinoma cells. We investigated the effect of 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (M1), a main intestinal bacterial metabolite of ginseng, on the NF-kappaB-dependent metastasis. M1 was effective in suppressing the TNF-alpha-induced activation of NF-kappaB, expression of matrix metalloprotease-9 (MMP-9), migration and invasion. The TNF-alpha-evoked increase in lung and liver metastasis of colon carcinoma was also abrogated by treatment with M1 in vitro. These results suggest that ginseng has potential to suppress inflammation-related metastasis by downregulating the NF-kappaB signaling pathway.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Movement; Colonic Neoplasms; Female; Ginsenosides; Liver Neoplasms; Lung Neoplasms; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; NF-kappa B; Signal Transduction; Tumor Necrosis Factor-alpha

The in vitro antitumor activity of a novel ginseng saponin metabolite, 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (IH-901), was examined against four human cancer cell lines and one subline resistant to cisplatin (CDDP). The growth inhibitory activity of the compound was estimated by MTT tetrazolium assay. The mean concentrations of IH-901 needed to inhibit the proliferation of the cells by 50% (IC50) were 24.3, 25.9, 56.6 and 24.9 microM against human myeloid leukemia (HL-60), pulmonary adenocarcinoma (PC-14), gastric adenocarcinoma (MKN-45) and hepatoma (HepG2) cell lines, respectively. These values are higher than that of CDDP. In the CDDP-resistant PC/DDP cell line, the IC50 values of IH-901 and CDDP were 20.3 and 60.8 microM, respectively. These results suggest that IH-901 is not cross-resistant to CDDP in this cell line and could be a candidate for the treatment of CDDP resistant pulmonary cancer.

Topics: Adenocarcinoma; Antineoplastic Agents; Cisplatin; Drug Resistance, Neoplasm; Ginsenosides; Humans; Lung Neoplasms; Saponins; Triterpenes; Tumor Cells, Cultured