ginsenoside-rg3 and Multiple-Myeloma

Ginsenoside Rg3 (Rg3) is one of the primary constituents isolated from ginseng, and has been found to exhibit cytotoxic effects against cancer cells. The present study aimed to investigate the effects of Rg3 on human multiple myeloma cell proliferation and apoptosis, and to examine its underlying molecular mechanisms. Cell viability was detected using a Cell Counting kit‑8 assay, and cell cycle arrest and cell apoptosis were analyzed using flow cytometry. In addition, the expression levels of cell cycle‑associated markers and apoptosis‑associated proteins, and the release of cytochrome C were determined using western blot analysis. The effects of Rg3 on the insulin‑like growth factor (IGF)-1/AKT/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase signaling pathways were also investigated using western blot analysis. The results showed that Rg3 inhibited cell viability in U266, RPMI8226 and SKO‑007 cells in a time‑ and dose‑dependent manner, and caused cell cycle arrest in the G1 phase by regulating the cyclin‑dependent kinase pathway. Furthermore, Rg3 induced multiple myeloma cell apoptosis, and was involved in B cell lymphoma-2 (Bcl2)/Bcl2-associated X protein imbalance, caspase activation and the release of cytochrome C from the mitochondria into the cytoplasm. Mechanistically, it was found that the inhibitory effects of Rg3 on multiple myeloma cell proliferation were essential for secretion of IGF‑1 and inactivation of the Akt/mTOR pathway. Collectively, these findings demonstrated that Rg3 effectively inhibited cell proliferation and induced apoptosis of multiple myeloma cells. These data broaden the clinical investigation of Rg3 in the treatment of multiple myeloma, associated with the inactivation of IGF-1/AKT/mTOR signaling.

Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Ginsenosides; Humans; Insulin-Like Growth Factor I; Mitochondria; Mitogen-Activated Protein Kinases; Multiple Myeloma; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases

Ginsenoside Rg3 is one of the main constituents isolated from Panax ginseng, and exhibits cytotoxic effects against cancer cells. The present study aimed to investigate the effects of ginsenoside Rg3 on human multiple myeloma cells, and determine the underlying molecular mechanisms. The cells were exposed to ginsenoside Rg3 at various concentrations (0‑80 µM) for 48 h. A subsequent cell proliferation assay demonstrated that treatment with ginsenoside Rg3 resulted in a dose‑dependent inhibition of the proliferation of U266 and RPMI8226 cells. Furthermore, exposure to ginsenoside Rg3 led to a marked increase in the rate of apoptosis in the U266 cells, coupled with increased caspase‑3 activity. The ginsenoside Rg3‑treated cells also exhibited an elevation in the expression of B‑cell lymphoma 2‑associated X protein (Bax), a pro‑apoptotic protein. Notably, knockdown of Bax protected the U266 cells from Rg3‑induced apoptosis. Overall, these findings suggested that ginsenoside Rg3 induced apoptosis in multiple myeloma cells, at least partially, through upregulation of the expression of Bax.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Ginsenosides; Humans; Multiple Myeloma; Panax

To explore the effect of 20 (S)-ginsenoside Rg3 [20 (S)-Rg3] on the proliferation inhibition and secretion of vascular endothelial growth factor (VEGF) of multiple myeloma (MM) cell line U266.. The proliferation inhibition rate of U266 cells after treatment with different doses of 20 (S)-Rg3 was detected by MTT method, the cell cycle and apoptosis by flow cytometry, the expression of apoptosis related proteins of caspase-3, 8 and 9 by Western blot, VEGF concentration in the culture supernatant by ELISA.. It showed that 20 (S)-Rg3 could inhibit the proliferation of U266 in a dose-dependent manner (P<0.05) with IC50 of (71.07 ± 2.63)μmol/L and (44.06 ± 3.98) μmol/L at 24 h and 48 h, respectively. VEGF concentration in the culture supernatant showed a dosedependent reduction (P<0.05), decreased from (419.93 ± 36.76) pg/106 cells in the control group to (314.82 ± 27.05) pg/106 cells in 80 μmol/L 20 (S)-Rg3 treated group by ELISA assay. Flow cytometry with Annexin-V/PI double staining revealed that 20(S)-Rg3 may induce U266 cells apoptosis in a concentration-dependent manner from (0.51 ± 0.05)% at control group to (8.32 ± 0.83)%, (10.72 ± 1.29)% and (15.27 ± 2.26)% at 20, 40 and 80 μmol/L treatment groups, respectively (P<0.05). Flow cytometry with PI staining showed that the ratio of cells in G0/G1 phase increased from (49.11 ± 1.71)% to (52.72 ± 7.75)%, (60.29 ± 5.76)% and (61.81 ± 3.46)%, respectively (P<0.05). Western blot analysis indicated that the expression of caspase-3, 8 and 9 declined, and that of cleaved-caspase-3, 8 and 9 significantly increased (P<0.05) with 20 (S)-Rg3 concentration increased.. 20(S)-Rg3 can inhibit the proliferation of U266 cells by cell cycle arrest in G1 phase and induce cell apoptosis by increasing the expressions of cleaved-caspase-3, -8 and -9. It can also inhibit VEGF secretion of U266 cells, which makes it a potential agent for multiple myeloma therapy.

Topics: Apoptosis; Caspases; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Ginsenosides; Humans; Multiple Myeloma; Vascular Endothelial Growth Factor A