ginsenoside-rg3 and Neoplasm-Metastasis

Invasion and metastasis are the major causes leading to the high mortality of colon cancer. Ginsenoside Rg3 (Rg3), as a bioactive ginseng compound, is suggested to possess antimetastasis effects in colon cancer. However, the underlying molecular mechanisms remain unclear. In this study, we reported that Rg3 could effectively inhibit colon cancer cell invasion and metastasis through

Topics: Animals; Antineoplastic Agents; Colonic Neoplasms; Down-Regulation; Epithelial-Mesenchymal Transition; Ginsenosides; Humans; Interleukin-6; Male; Mice, Inbred BALB C; Neoplasm Metastasis; Receptors, Notch; Signal Transduction; Transcription Factor HES-1; Tumor Cells, Cultured

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. The prognosis of HCC remains very poor; thus, an effective treatment remains urgent. Herein, a type of nanomedicine is developed by conjugating Fe@Fe

Topics: Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Ginsenosides; Humans; Liver Neoplasms; Mice; Nanoparticles; Neoplasm Metastasis

Ginsenoside Rg3, a bioactive constituent from Panax ginseng, is a worldwide well-known traditional Chinese medicine used as a tonic. It also has good antitumor activity by inhibiting tumors metastasis. Tumor metastasis is a high risk in thyroid cancer. However, the effect and molecular mechanism underlying the antimetastatic activity of Rg3 in thyroid cancer have not been reported. In our study, we found that Rg3 inhibited the growth of thyroid cancer in vitro and in vivo and significantly inhibited metastasis of thyroid cancer. Rg3 apparently inhibited the migration and invasion in four papillary thyroid cancer (PTC) cells (TPC-1, BCPAP, C643, and Ocut-2c cells) and pulmonary metastasis in lung metastasis model of C643 cells in nude mice. We further found that a possible mechanism of Rg3 inhibiting thyroid cancer cells metastasis was associated with inhibiting cells actin skeleton function. Rg3 inhibited lamellipodia formation and induced microspike formation by inhibiting Rho GTPase in thyroid cancer cells. Rg3 decreased the levels of Rac-1 and Cdc42 proteins. In addition, Rg3 decreased the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins in four thyroid cancer cells. The results that Rg3 remarkably inhibited the expression of vascular endothelial growth factor-C (VEGF-C) protein in PTC cells and VEGF-A protein in anaplastic thyroid cancer (ATC) cells and decreased the staining of CD31 in PTC and ATC tumors hinted that Rg3 might inhibit the lymph node metastasis in PTC and angiogenesis in ATC. These studies suggested that Rg3 might be a useful agent for the treatment of metastatic thyroid cancers.

Topics: Actins; Animals; Antineoplastic Agents, Phytogenic; cdc42 GTP-Binding Protein; Cell Line, Tumor; Cell Movement; Female; Ginsenosides; Humans; Lung Neoplasms; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mice, Nude; Neoplasm Metastasis; Panax; rac1 GTP-Binding Protein; Thyroid Neoplasms; Vascular Endothelial Growth Factor A

Ginsenoside Rg3 is a bioactive ginseng constituent that has been reported to have diverse pathological and physiological effects, including anti-inflammatory and anti-metastatic activities. Metastasis is one of the most important factors involved in patients with melanoma. However, the molecular mechanism underlying the anti-metastatic activities of Rg3 in malignant melanoma cancer has not been fully elucidated. In this study, we have evaluated that Rg3 effectively inhibits metastasis of B16F10 melanoma cancer cells. We found that Rg3 significantly suppresses the migration, invasion, wound healing, and colony-forming abilities of B16F10 cells in a dose-dependent manner. Mechanistically, we demonstrate that Rg3 suppresses B16F10 cell metastasis by inhibiting MMP-13 expression. These results indicate that Rg3 suppresses the metastasis of B16F10 mouse melanoma cancer cells via MMP-13 regulation. Importantly, MMP-13 downregulation may influence the migration and invasion capabilities of melanoma cells and has been correlated with melanoma progression. Therefore, Rg3 is a potential therapeutic candidate that could be used to treat patients with metastatic melanoma.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Drug; Ginsenosides; Matrix Metalloproteinase 13; Melanoma; Mice; Neoplasm Metastasis

The prognosis of patients with ovarian cancer has remained poor mainly because of aggressive cancer progression. Since epithelial-mesenchymal transition (EMT) is an important mechanism mediating invasion and metastasis of cancer cells, targeting the EMT process with more efficacious and less toxic compounds to inhibit metastasis is of great therapeutic value for the treatment of ovarian cancer. We have found for the first time that the ginsenoside 20(S)-Rg3, a pharmacologically active component of the traditional Chinese herb Panax ginseng, potently blocks hypoxia-induced EMT of ovarian cancer cells in vitro and in vivo. Mechanistic studies confirm the mode of action of 20(S)-Rg3, which reduces the expression of hypoxia-inducible factor 1α (HIF-1α) by activating the ubiquitin-proteasome pathway to promote HIF-1α degradation. A decrease in HIF-1α in turn leads to up-regulation, via transcriptional suppression of Snail, of the epithelial cell-specific marker E-cadherin and down-regulation of the mesenchymal cell-specific marker vimentin under hypoxic conditions. Importantly, 20(S)-Rg3 effectively inhibits EMT in nude mouse xenograft models of ovarian cancer, promising a novel therapeutic agent for anticancer therapy.

Topics: Animals; Cell Hypoxia; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Female; Ginsenosides; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Ovarian Neoplasms; Proteolysis; Xenograft Model Antitumor Assays

To study the effect of angiogenesis inhibitor Rg3 on the growth and metastasis of gastric cancer in SCID mice.. Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of SCID mice. Rg3 was administered by gastric perfusion at doses of 0, 2.5, 5.0, 10.0 mg/kg every day for 6 weeks 1 week after tumor implantation. One week after last administration, the mice were killed and their tumor weight was measured and the presence of metastasis recorded. Intratumoral microvessel density was examined by immunohistochemical staining with anti-CD31 monoclonal antibody.. Compared to the untreated controls, the growth of the orthotopically implanted tumor was significantly reduced in weight in mice treated with Rg3 with an inhibition rate of 52.3%, 63.3% and 71.6% at doses of 2.5, 5.0, 10.0 mg/kg, respectively. Tumor metastasis to the liver and peritoneum was also significantly inhibited in a dose-dependent manner. Decreased intratumoral microvessel density was noted in the treated mice.. Angiogenesis inhibitor Rg3 has strong inhibitory effect on tumor growth and metastasis of human gastric cancer in SCID mice.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Female; Ginsenosides; Humans; Mice; Mice, SCID; Neoplasm Metastasis; Stomach Neoplasms

The effects of concomitant use of bombesin and ginsenoside Rg3 on the incidence of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane were investigated in male inbred Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and s.c. injection of bombesin (40 microg/kg body weight) every other day, and from week 20, s.c. injections of ginsenoside Rg3 (2.5 or 5.0 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of a higher dose of ginsenoside Rg3 with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth pattern, labeling and apoptotic indices and tumor vascularity of intestinal cancers, it significantly decreased the incidence of cancer metastasis. These findings indicate that ginsenoside Rg3 inhibits cancer metastasis through activities that do not affect the growth or vascularity of intestinal cancers.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Apoptosis; Azoxymethane; Bombesin; Carcinogens; Ginsenosides; Intestinal Neoplasms; Male; Neoplasm Metastasis; Peritoneal Neoplasms; Rats; Rats, Wistar; Saponins

The effect of plant glycosides on tumor cell invasion was examined. Among the glycosides tested, ginsenoside Rg3 was found to be a potent inhibitor of invasion by rat ascites hepatoma cells (MM1), B16FE7 melanoma cells, human small cell lung carcinoma (OC10), and human pancreatic adenocarcinoma (PSN-1) cells, when examined in a cell monolayer invasion model. Structurally analogous ginsenosides, Rb2, 20(R)-ginsenoside Rg2 and 20(S)-ginsenoside Rg3 (a stereoisomer of Rg3), showed little inhibitory activity. Neither Rh1, Rh2, 20(R)-ginsenosides Rh1, Rb1, Rc nor Re had any effect. The effective ginsenoside, Rg3, tended to inhibit experimental pulmonary metastasis by highly metastatic mouse melanoma B16FE7 cells as well. Taking account of our previous finding that 1-oleoyl-lysophosphatidic add (LPA) induced invasion by MM1 cells in the monolayer invasion model, the effect of Rg3 on molecular events associated with the invasion induced by LPA was analyzed in order to understand the mechanism of the inhibition. Rg3, which suppressed the invasion induced by LPA, dose-dependently inhibited the LPA-triggered rise of intracellular Ca2+. Protein tyrosine phosphorylation triggered by LPA was not inhibited by Rg3.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Carbohydrate Sequence; Carcinoma, Small Cell; Ginsenosides; Humans; Liver Neoplasms, Experimental; Lung Neoplasms; Lysophospholipids; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Pancreatic Neoplasms; Phosphorylation; Rats; Rats, Inbred Strains; Saponins; Tyrosine

We examined the inhibitory effect of two saponin preparations from Red ginseng, 20(R)- and 20(S)-ginsenoside-Rg3, in comparison with that of ginsenoside-Rb2, on lung metastasis produced by two highly metastatic tumor cells, B16-BL6 melanoma and colon 26-M3.1 carcinoma, in syngeneic mice. In an in vitro analysis, both saponin preparations showed a significant inhibition of adhesion to fibronectin (FN) and laminin (LM) by B16-BL6 melanoma. Similarly, they significantly inhibited the invasion of B16-BL6 cells into the reconstituted basement membrane (Matrigel)/FN in a dose-dependent manner. In an experimental metastasis model using B16-BL6 melanoma, consecutive intravenous (i.v.) administrations of 100 micrograms/mouse of 20(R)- or 20(S)-ginsenoside-Rg3 1, 2, 3 and 4 d after tumor inoculation led to a significant decrease in lung metastasis. The inhibitory effect of i.v. administration of both ginseng saponins on the tumor metastasis of B16-BL6 melanoma was also recognized in a low dose of 10 micrograms/mouse. The oral administration (p.o.) of both saponins (100-1000 micrograms/mouse) induced a significant decrease in lung metastasis of B16-BL6 melanoma. Moreover, both ginseng saponins were effective in inhibiting of lung metastasis produced by colon 26-M3.1 carcinoma. When 20(R)- or 20(S)-ginsenoside-Rg3 was orally administered consecutively after tumor inoculation in a spontaneous metastasis model using B16-BL6 melanoma, both of them significantly inhibited lung metastasis. In the experiment involving neovasculization by tumor cells in vivo, both mice groups given each saponin preparation after tumor inoculation exhibited a significant decrease in the number of blood vessels oriented toward the tumor mass, with no repression of tumor size. These findings suggest that both ginseng saponins, 20(R)- and 20(S)-ginsenoside-Rg3, possess an ability to inhibit the lung metastasis of tumor cells, and the mechanism of their antimetastatic effect is related to inhibition of the adhesion and invasion of tumor cells, and also to anti-angiogenesis activity.

Topics: Animals; Antineoplastic Agents; Cell Adhesion; Female; Ginsenosides; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Metastasis; Neovascularization, Pathologic; Panax; Plants, Medicinal; Saponins; Stereoisomerism; Tumor Cells, Cultured