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Oleanolic acid induces mitochondrial-dependent apoptosis and G0/G1 phase arrest in gallbladder cancer cells.

Li HF, Wang XA, Xiang SS, Hu YP, Jiang L, Shu YJ, Li ML, Wu XS, Zhang F, Ye YY, Weng H, Bao RF, Cao Y, Lu W, Dong Q, Liu YB - Drug Des Devel Ther (2015)

Bottom Line: Unfortunately, the effects of OA on gallbladder carcinoma are unknown.In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism.Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma.

View Article: PubMed Central - PubMed

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

ABSTRACT
Oleanolic acid (OA), a naturally occurring triterpenoid, exhibits potential antitumor activity in many tumor cell lines. Gallbladder carcinoma is the most common malignancy of the biliary tract, and is a highly aggressive tumor with an extremely poor prognosis. Unfortunately, the effects of OA on gallbladder carcinoma are unknown. In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism. The results showed that OA inhibits proliferation of gallbladder cancer cells in a dose-dependent and time-dependent manner on MTT and colony formation assay. A flow cytometry assay revealed apoptosis and G0/G1 phase arrest in GBC-SD and NOZ cells. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. Moreover, this drug inhibited tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data suggest that OA inhibits proliferation of gallbladder cancer cells by regulating apoptosis and the cell cycle process. Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma.

No MeSH data available.


Related in: MedlinePlus

Oleanolic acid inhibits proliferation and viability of gallbladder cancer cells.Notes: (A) Cell viability and IC50 were measured by MTT assay. (B) GBC-SD and NOZ cells were treated with various concentrations of oleanolic acid (0, 3, 6, and 9 μmol/L) for 48 hours and then allowed to form colonies in fresh medium without oleanolic acid for 14 days. (C) Detailed information on colony formation is shown. All data are presented as the mean ± standard deviation and are from three independent experiments. *P<0.05, **P<0.01 versus the control group.
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f2-dddt-9-3017: Oleanolic acid inhibits proliferation and viability of gallbladder cancer cells.Notes: (A) Cell viability and IC50 were measured by MTT assay. (B) GBC-SD and NOZ cells were treated with various concentrations of oleanolic acid (0, 3, 6, and 9 μmol/L) for 48 hours and then allowed to form colonies in fresh medium without oleanolic acid for 14 days. (C) Detailed information on colony formation is shown. All data are presented as the mean ± standard deviation and are from three independent experiments. *P<0.05, **P<0.01 versus the control group.

Mentions: The MTT assay were carried out to test cell proliferation. Treatment with OA resulted in a marked decrease in viability of GBC-SD and NOZ cells in a dose-dependent and time-dependent manner (Figure 2A). The half maximal inhibitory concentration (IC50) of the GBC-SD and NOZ cells at 48 hours was approximately 50 μmol/L. According to the curve, we chose 30, 60, and 90 μmol/L as the optimum concentration range for both cell lines in the subsequent experiments, and the effects of OA at 48 hours were more obvious and stable than at 24 hours and 72 hours, so groups at 48 hours were chosen to detect changes in molecular events during the subsequent experiments. The ability of GBC-SD and NOZ cells to form colonies in the presence of OA was assessed by the flat plate colony formation assay (Figure 2B). The colony count indicated that OA induced a dose-dependent decrease in colony formation ability. Moreover, statistical analysis demonstrated that the mean sizes of the control colonies were significantly larger than those of the OA-treated groups (Figure 2C). These findings demonstrate that OA significantly inhibits the viability and proliferation of GBC-SD and NOZ cells.


Oleanolic acid induces mitochondrial-dependent apoptosis and G0/G1 phase arrest in gallbladder cancer cells.

Li HF, Wang XA, Xiang SS, Hu YP, Jiang L, Shu YJ, Li ML, Wu XS, Zhang F, Ye YY, Weng H, Bao RF, Cao Y, Lu W, Dong Q, Liu YB - Drug Des Devel Ther (2015)

Oleanolic acid inhibits proliferation and viability of gallbladder cancer cells.Notes: (A) Cell viability and IC50 were measured by MTT assay. (B) GBC-SD and NOZ cells were treated with various concentrations of oleanolic acid (0, 3, 6, and 9 μmol/L) for 48 hours and then allowed to form colonies in fresh medium without oleanolic acid for 14 days. (C) Detailed information on colony formation is shown. All data are presented as the mean ± standard deviation and are from three independent experiments. *P<0.05, **P<0.01 versus the control group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4472077&req=5

f2-dddt-9-3017: Oleanolic acid inhibits proliferation and viability of gallbladder cancer cells.Notes: (A) Cell viability and IC50 were measured by MTT assay. (B) GBC-SD and NOZ cells were treated with various concentrations of oleanolic acid (0, 3, 6, and 9 μmol/L) for 48 hours and then allowed to form colonies in fresh medium without oleanolic acid for 14 days. (C) Detailed information on colony formation is shown. All data are presented as the mean ± standard deviation and are from three independent experiments. *P<0.05, **P<0.01 versus the control group.
Mentions: The MTT assay were carried out to test cell proliferation. Treatment with OA resulted in a marked decrease in viability of GBC-SD and NOZ cells in a dose-dependent and time-dependent manner (Figure 2A). The half maximal inhibitory concentration (IC50) of the GBC-SD and NOZ cells at 48 hours was approximately 50 μmol/L. According to the curve, we chose 30, 60, and 90 μmol/L as the optimum concentration range for both cell lines in the subsequent experiments, and the effects of OA at 48 hours were more obvious and stable than at 24 hours and 72 hours, so groups at 48 hours were chosen to detect changes in molecular events during the subsequent experiments. The ability of GBC-SD and NOZ cells to form colonies in the presence of OA was assessed by the flat plate colony formation assay (Figure 2B). The colony count indicated that OA induced a dose-dependent decrease in colony formation ability. Moreover, statistical analysis demonstrated that the mean sizes of the control colonies were significantly larger than those of the OA-treated groups (Figure 2C). These findings demonstrate that OA significantly inhibits the viability and proliferation of GBC-SD and NOZ cells.

Bottom Line: Unfortunately, the effects of OA on gallbladder carcinoma are unknown.In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism.Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma.

View Article: PubMed Central - PubMed

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

ABSTRACT
Oleanolic acid (OA), a naturally occurring triterpenoid, exhibits potential antitumor activity in many tumor cell lines. Gallbladder carcinoma is the most common malignancy of the biliary tract, and is a highly aggressive tumor with an extremely poor prognosis. Unfortunately, the effects of OA on gallbladder carcinoma are unknown. In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism. The results showed that OA inhibits proliferation of gallbladder cancer cells in a dose-dependent and time-dependent manner on MTT and colony formation assay. A flow cytometry assay revealed apoptosis and G0/G1 phase arrest in GBC-SD and NOZ cells. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. Moreover, this drug inhibited tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data suggest that OA inhibits proliferation of gallbladder cancer cells by regulating apoptosis and the cell cycle process. Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma.

No MeSH data available.


Related in: MedlinePlus