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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 induces apoptosis in gallbladder cancer cells.Notes: (A) GBC-SD and NOZ cells treated with OA (0, 30, 60, and 90 μmol/L) for 48 hours were stained with Annexin V-FITC/PI and analyzed by flow cytometry. (B) The percentage of apoptotic cells is presented as the mean ± standard deviation. (C) Changes in apoptotic nuclear morphology were observed by Hoechst 33342 staining and visualized by fluorescent microscopy. The results shown are representative of data from three independent experiments. *P<0.05, **P<0.01, ***P<0.001 versus the control group.Abbreviations: FITC, fluorescein isothiocyanate; OA, oleanolic acid; PI, propidium iodide.
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f3-dddt-9-3017: Oleanolic acid induces apoptosis in gallbladder cancer cells.Notes: (A) GBC-SD and NOZ cells treated with OA (0, 30, 60, and 90 μmol/L) for 48 hours were stained with Annexin V-FITC/PI and analyzed by flow cytometry. (B) The percentage of apoptotic cells is presented as the mean ± standard deviation. (C) Changes in apoptotic nuclear morphology were observed by Hoechst 33342 staining and visualized by fluorescent microscopy. The results shown are representative of data from three independent experiments. *P<0.05, **P<0.01, ***P<0.001 versus the control group.Abbreviations: FITC, fluorescein isothiocyanate; OA, oleanolic acid; PI, propidium iodide.

Mentions: The apoptotic effects of OA on GBC-SD and NOZ cells were investigated by measuring the binding of Annexin V-FITC/PI staining. As assessed by flow cytometry and shown in Figure 3A, OA reduced the number of surviving cells and increased the number of both early and late apoptotic cells in a dose-dependent manner (Figure 3B).


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 induces apoptosis in gallbladder cancer cells.Notes: (A) GBC-SD and NOZ cells treated with OA (0, 30, 60, and 90 μmol/L) for 48 hours were stained with Annexin V-FITC/PI and analyzed by flow cytometry. (B) The percentage of apoptotic cells is presented as the mean ± standard deviation. (C) Changes in apoptotic nuclear morphology were observed by Hoechst 33342 staining and visualized by fluorescent microscopy. The results shown are representative of data from three independent experiments. *P<0.05, **P<0.01, ***P<0.001 versus the control group.Abbreviations: FITC, fluorescein isothiocyanate; OA, oleanolic acid; PI, propidium iodide.
© Copyright Policy
Related In: Results  -  Collection

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

f3-dddt-9-3017: Oleanolic acid induces apoptosis in gallbladder cancer cells.Notes: (A) GBC-SD and NOZ cells treated with OA (0, 30, 60, and 90 μmol/L) for 48 hours were stained with Annexin V-FITC/PI and analyzed by flow cytometry. (B) The percentage of apoptotic cells is presented as the mean ± standard deviation. (C) Changes in apoptotic nuclear morphology were observed by Hoechst 33342 staining and visualized by fluorescent microscopy. The results shown are representative of data from three independent experiments. *P<0.05, **P<0.01, ***P<0.001 versus the control group.Abbreviations: FITC, fluorescein isothiocyanate; OA, oleanolic acid; PI, propidium iodide.
Mentions: The apoptotic effects of OA on GBC-SD and NOZ cells were investigated by measuring the binding of Annexin V-FITC/PI staining. As assessed by flow cytometry and shown in Figure 3A, OA reduced the number of surviving cells and increased the number of both early and late apoptotic cells in a dose-dependent manner (Figure 3B).

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