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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 inhibits the viability and proliferation of GBC cells.Notes: Cell viability was assessed using an MTT assay. (A–C) Five human GBC cell lines were treated with 20(S)-Rg3 at different concentrations (0, 25, 50, 100, 200, and 400 μM) for 24, 48, and 72 hours. (D) Five human GBC cell lines were treated with 100 μM 20(S)-Rg3 for 24, 48, and 72 hours. (E) Representative photographs of colony formation are shown. 20(S)-Rg3 caused a concentration-dependent decrease in both colony numbers (F) and colony size (G). Data represent the mean ± SD of three independent experiments. *P<0.05, **P<0.01, ***P<0.001 vs control.Abbreviations: GBC, gallbladder cancer; SD, standard deviation; vs, versus; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide.
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f1-dddt-9-3969: 20(S)-Rg3 inhibits the viability and proliferation of GBC cells.Notes: Cell viability was assessed using an MTT assay. (A–C) Five human GBC cell lines were treated with 20(S)-Rg3 at different concentrations (0, 25, 50, 100, 200, and 400 μM) for 24, 48, and 72 hours. (D) Five human GBC cell lines were treated with 100 μM 20(S)-Rg3 for 24, 48, and 72 hours. (E) Representative photographs of colony formation are shown. 20(S)-Rg3 caused a concentration-dependent decrease in both colony numbers (F) and colony size (G). Data represent the mean ± SD of three independent experiments. *P<0.05, **P<0.01, ***P<0.001 vs control.Abbreviations: GBC, gallbladder cancer; SD, standard deviation; vs, versus; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide.

Mentions: To evaluate the toxic effect of 20(S)-Rg3 on GBC, five human GBC cell lines were treated with 20(S)-Rg3 at different concentrations (0, 0.1, 1, 10, 100, and 1,000 μM) for 24 and 48 hours. MTT assay showed that 20(S)-Rg3 exhibited a concentration-dependent and time-dependent killing of diverse GBC cell lines, with an IC50 (half maximal inhibitory concentration) value of around 100 μM (Figure S1A and B). Therefore, GBC cells were treated with 20(S)-Rg3 in the range of the drug concentrations (25–400 μM) in vitro. GBC-SD cell line was more sensitive to 20(S)-Rg3 than other cell lines, while NOZ cell line was less sensitive compared to other cell lines (Figure 1A–D). Besides, the proliferative rate of GBC-SD cell line was much lower than other cell lines, while that of NOZ cell line was much higher (Figure S1C). Therefore, NOZ and GBC-SD cell lines were chosen as optimal cell models for subsequent functional analyses.


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 inhibits the viability and proliferation of GBC cells.Notes: Cell viability was assessed using an MTT assay. (A–C) Five human GBC cell lines were treated with 20(S)-Rg3 at different concentrations (0, 25, 50, 100, 200, and 400 μM) for 24, 48, and 72 hours. (D) Five human GBC cell lines were treated with 100 μM 20(S)-Rg3 for 24, 48, and 72 hours. (E) Representative photographs of colony formation are shown. 20(S)-Rg3 caused a concentration-dependent decrease in both colony numbers (F) and colony size (G). Data represent the mean ± SD of three independent experiments. *P<0.05, **P<0.01, ***P<0.001 vs control.Abbreviations: GBC, gallbladder cancer; SD, standard deviation; vs, versus; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide.
© Copyright Policy
Related In: Results  -  Collection

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

f1-dddt-9-3969: 20(S)-Rg3 inhibits the viability and proliferation of GBC cells.Notes: Cell viability was assessed using an MTT assay. (A–C) Five human GBC cell lines were treated with 20(S)-Rg3 at different concentrations (0, 25, 50, 100, 200, and 400 μM) for 24, 48, and 72 hours. (D) Five human GBC cell lines were treated with 100 μM 20(S)-Rg3 for 24, 48, and 72 hours. (E) Representative photographs of colony formation are shown. 20(S)-Rg3 caused a concentration-dependent decrease in both colony numbers (F) and colony size (G). Data represent the mean ± SD of three independent experiments. *P<0.05, **P<0.01, ***P<0.001 vs control.Abbreviations: GBC, gallbladder cancer; SD, standard deviation; vs, versus; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide.
Mentions: To evaluate the toxic effect of 20(S)-Rg3 on GBC, five human GBC cell lines were treated with 20(S)-Rg3 at different concentrations (0, 0.1, 1, 10, 100, and 1,000 μM) for 24 and 48 hours. MTT assay showed that 20(S)-Rg3 exhibited a concentration-dependent and time-dependent killing of diverse GBC cell lines, with an IC50 (half maximal inhibitory concentration) value of around 100 μM (Figure S1A and B). Therefore, GBC cells were treated with 20(S)-Rg3 in the range of the drug concentrations (25–400 μM) in vitro. GBC-SD cell line was more sensitive to 20(S)-Rg3 than other cell lines, while NOZ cell line was less sensitive compared to other cell lines (Figure 1A–D). Besides, the proliferative rate of GBC-SD cell line was much lower than other cell lines, while that of NOZ cell line was much higher (Figure S1C). Therefore, NOZ and GBC-SD cell lines were chosen as optimal cell models for subsequent functional analyses.

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