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20(S)-ginsenoside Rg3 promotes senescence and apoptosis in gallbladder cancer cells via the p53 pathway.

Zhang F, Li M, Wu X, Hu Y, Cao Y, Wang X, Xiang S, Li H, Jiang L, Tan Z, Lu W, Weng H, Shu Y, Gong W, Wang X, Zhang Y, Shi W, Dong P, Gu J, Liu Y - Drug Des Devel Ther (2015)

Bottom Line: However, the anticancer effect of 20(S)-Rg3 in human GBC has not yet been determined.In this study, we primarily found that 20(S)-Rg3 exposure suppressed the survival of both NOZ and GBC-SD cell lines in a concentration-dependent manner.Our results demonstrated that 20(S)-Rg3 potently inhibited growth and survival of GBC cells both in vitro and in vivo. 20(S)-Rg3 attenuated GBC growth probably via activation of the p53 pathway, and subsequent induction of cellular senescence and mitochondrial-dependent apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
Gallbladder cancer (GBC), the most frequent malignancy of the biliary tract, is associated with high mortality and extremely poor prognosis. 20(S)-ginsenoside Rg3 (20(S)-Rg3) is a steroidal saponin with high pharmacological activity. However, the anticancer effect of 20(S)-Rg3 in human GBC has not yet been determined. In this study, we primarily found that 20(S)-Rg3 exposure suppressed the survival of both NOZ and GBC-SD cell lines in a concentration-dependent manner. Moreover, induction of cellular senescence and G0/G1 arrest by 20(S)-Rg3 were accompanied by a large accumulation of p53 and p21 as a result of murine double minute 2 (MDM2) inhibition. 20(S)-Rg3 also caused a remarkable increase in apoptosis via the activation of the mitochondrial-mediated intrinsic caspase pathway. Furthermore, intraperitoneal injection of 20(S)-Rg3 (20 or 40 mg/kg) for 3 weeks markedly inhibited the growth of xenografts in nude mice. Our results demonstrated that 20(S)-Rg3 potently inhibited growth and survival of GBC cells both in vitro and in vivo. 20(S)-Rg3 attenuated GBC growth probably via activation of the p53 pathway, and subsequent induction of cellular senescence and mitochondrial-dependent apoptosis. Therefore, 20(S)-Rg3 may be a potential chemotherapeutic agent for GBC therapy.

No MeSH data available.


Related in: MedlinePlus

20(S)-Rg3 blocks the cell cycle progression of gallbladder cancer cells.Notes: (A, B) The cell cycle phases of the treated cells were evaluated by flow cytometry. (C) Western blot analysis of cell cycle-related proteins in both cell lines. β-actin was used as a loading control. Data represent the mean ± SD of three independent experiments.Abbreviation: SD, standard deviation
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f3-dddt-9-3969: 20(S)-Rg3 blocks the cell cycle progression of gallbladder cancer cells.Notes: (A, B) The cell cycle phases of the treated cells were evaluated by flow cytometry. (C) Western blot analysis of cell cycle-related proteins in both cell lines. β-actin was used as a loading control. Data represent the mean ± SD of three independent experiments.Abbreviation: SD, standard deviation

Mentions: Cellular senescence, which can be defined as a stress response preventing the propagation of cells that have accumulated potentially oncogenic alterations, is invariably associated with a permanent cell cycle arrest. To determine whether cell cycle arrest is responsible for 20(S)-Rg3-induced decrease in cell viability, flow cytometry was performed, which showed that the percentage of cells in G0/G1 phase was significantly increased in both cell lines following 20(S)-Rg3 treatment, while cell populations in S phase and G2/M phase were simultaneously reduced (Figure 3A and B). These results indicate that 20(S)-Rg3 could arrest the cell cycle at G0/G1 phase in a dose-dependent manner. Western blot further confirmed that the levels of the S-related protein Cyclin A and the G2/M-related protein Cyclin B1 were down-regulated in NOZ and GBC-SD cells following 20(S)-Rg3 treatment (Figure 3C).


20(S)-ginsenoside Rg3 promotes senescence and apoptosis in gallbladder cancer cells via the p53 pathway.

Zhang F, Li M, Wu X, Hu Y, Cao Y, Wang X, Xiang S, Li H, Jiang L, Tan Z, Lu W, Weng H, Shu Y, Gong W, Wang X, Zhang Y, Shi W, Dong P, Gu J, Liu Y - Drug Des Devel Ther (2015)

20(S)-Rg3 blocks the cell cycle progression of gallbladder cancer cells.Notes: (A, B) The cell cycle phases of the treated cells were evaluated by flow cytometry. (C) Western blot analysis of cell cycle-related proteins in both cell lines. β-actin was used as a loading control. Data represent the mean ± SD of three independent experiments.Abbreviation: SD, standard deviation
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539091&req=5

f3-dddt-9-3969: 20(S)-Rg3 blocks the cell cycle progression of gallbladder cancer cells.Notes: (A, B) The cell cycle phases of the treated cells were evaluated by flow cytometry. (C) Western blot analysis of cell cycle-related proteins in both cell lines. β-actin was used as a loading control. Data represent the mean ± SD of three independent experiments.Abbreviation: SD, standard deviation
Mentions: Cellular senescence, which can be defined as a stress response preventing the propagation of cells that have accumulated potentially oncogenic alterations, is invariably associated with a permanent cell cycle arrest. To determine whether cell cycle arrest is responsible for 20(S)-Rg3-induced decrease in cell viability, flow cytometry was performed, which showed that the percentage of cells in G0/G1 phase was significantly increased in both cell lines following 20(S)-Rg3 treatment, while cell populations in S phase and G2/M phase were simultaneously reduced (Figure 3A and B). These results indicate that 20(S)-Rg3 could arrest the cell cycle at G0/G1 phase in a dose-dependent manner. Western blot further confirmed that the levels of the S-related protein Cyclin A and the G2/M-related protein Cyclin B1 were down-regulated in NOZ and GBC-SD cells following 20(S)-Rg3 treatment (Figure 3C).

Bottom Line: However, the anticancer effect of 20(S)-Rg3 in human GBC has not yet been determined.In this study, we primarily found that 20(S)-Rg3 exposure suppressed the survival of both NOZ and GBC-SD cell lines in a concentration-dependent manner.Our results demonstrated that 20(S)-Rg3 potently inhibited growth and survival of GBC cells both in vitro and in vivo. 20(S)-Rg3 attenuated GBC growth probably via activation of the p53 pathway, and subsequent induction of cellular senescence and mitochondrial-dependent apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
Gallbladder cancer (GBC), the most frequent malignancy of the biliary tract, is associated with high mortality and extremely poor prognosis. 20(S)-ginsenoside Rg3 (20(S)-Rg3) is a steroidal saponin with high pharmacological activity. However, the anticancer effect of 20(S)-Rg3 in human GBC has not yet been determined. In this study, we primarily found that 20(S)-Rg3 exposure suppressed the survival of both NOZ and GBC-SD cell lines in a concentration-dependent manner. Moreover, induction of cellular senescence and G0/G1 arrest by 20(S)-Rg3 were accompanied by a large accumulation of p53 and p21 as a result of murine double minute 2 (MDM2) inhibition. 20(S)-Rg3 also caused a remarkable increase in apoptosis via the activation of the mitochondrial-mediated intrinsic caspase pathway. Furthermore, intraperitoneal injection of 20(S)-Rg3 (20 or 40 mg/kg) for 3 weeks markedly inhibited the growth of xenografts in nude mice. Our results demonstrated that 20(S)-Rg3 potently inhibited growth and survival of GBC cells both in vitro and in vivo. 20(S)-Rg3 attenuated GBC growth probably via activation of the p53 pathway, and subsequent induction of cellular senescence and mitochondrial-dependent apoptosis. Therefore, 20(S)-Rg3 may be a potential chemotherapeutic agent for GBC therapy.

No MeSH data available.


Related in: MedlinePlus