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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 exhibits an anticancer effect in vivo.Notes: (A) NOZ cells were subcutaneously injected into the right flank of nude mice. The mice were then administered 0.2 mL of vehicle (10% dimethyl sulfoxide and 90% phosphate-buffered saline) or OA (75, 150 mg/kg) intraperitoneally every 2 days for up to 15 days. Photographs of five representative mice (n=10) from each group are presented to show the sizes of the resulting tumors. (B, C) Tumors were excised from the animals and weighed. (D) Hematoxylineosin staining and IHC staining of Ki-67 in xenograft tumors. (E) Scoring of Ki-67 IHC staining. **P<0.01 versus the control group.Abbreviations: OA, oleanolic acid; HE, hematoxylineosin; IHC, immunohistochemistry.
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f7-dddt-9-3017: Oleanolic acid exhibits an anticancer effect in vivo.Notes: (A) NOZ cells were subcutaneously injected into the right flank of nude mice. The mice were then administered 0.2 mL of vehicle (10% dimethyl sulfoxide and 90% phosphate-buffered saline) or OA (75, 150 mg/kg) intraperitoneally every 2 days for up to 15 days. Photographs of five representative mice (n=10) from each group are presented to show the sizes of the resulting tumors. (B, C) Tumors were excised from the animals and weighed. (D) Hematoxylineosin staining and IHC staining of Ki-67 in xenograft tumors. (E) Scoring of Ki-67 IHC staining. **P<0.01 versus the control group.Abbreviations: OA, oleanolic acid; HE, hematoxylineosin; IHC, immunohistochemistry.

Mentions: To further determine if OA inhibits tumor growth in vivo and confirm its safety, vehicle (10% DMSO and 90% PBS) or OA (75 mg/kg, 150 mg/kg) were injected into nude mice carrying subcutaneous NOZ tumor xenografts every 2 days for up to 15 days.15 Tumors removed from these mice are shown in Figure 7A and B, and their mean weights are shown in Figure 7C. Tumors from OA-treated mice were clearly smaller and lighter than those of mice in the vehicle group, indicating that OA inhibited tumor growth in mice in a dose-dependent manner. At the same time, no side effects were observed in the mice treated with OA, and all of the animals survived the experiment.


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 exhibits an anticancer effect in vivo.Notes: (A) NOZ cells were subcutaneously injected into the right flank of nude mice. The mice were then administered 0.2 mL of vehicle (10% dimethyl sulfoxide and 90% phosphate-buffered saline) or OA (75, 150 mg/kg) intraperitoneally every 2 days for up to 15 days. Photographs of five representative mice (n=10) from each group are presented to show the sizes of the resulting tumors. (B, C) Tumors were excised from the animals and weighed. (D) Hematoxylineosin staining and IHC staining of Ki-67 in xenograft tumors. (E) Scoring of Ki-67 IHC staining. **P<0.01 versus the control group.Abbreviations: OA, oleanolic acid; HE, hematoxylineosin; IHC, immunohistochemistry.
© Copyright Policy
Related In: Results  -  Collection

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

f7-dddt-9-3017: Oleanolic acid exhibits an anticancer effect in vivo.Notes: (A) NOZ cells were subcutaneously injected into the right flank of nude mice. The mice were then administered 0.2 mL of vehicle (10% dimethyl sulfoxide and 90% phosphate-buffered saline) or OA (75, 150 mg/kg) intraperitoneally every 2 days for up to 15 days. Photographs of five representative mice (n=10) from each group are presented to show the sizes of the resulting tumors. (B, C) Tumors were excised from the animals and weighed. (D) Hematoxylineosin staining and IHC staining of Ki-67 in xenograft tumors. (E) Scoring of Ki-67 IHC staining. **P<0.01 versus the control group.Abbreviations: OA, oleanolic acid; HE, hematoxylineosin; IHC, immunohistochemistry.
Mentions: To further determine if OA inhibits tumor growth in vivo and confirm its safety, vehicle (10% DMSO and 90% PBS) or OA (75 mg/kg, 150 mg/kg) were injected into nude mice carrying subcutaneous NOZ tumor xenografts every 2 days for up to 15 days.15 Tumors removed from these mice are shown in Figure 7A and B, and their mean weights are shown in Figure 7C. Tumors from OA-treated mice were clearly smaller and lighter than those of mice in the vehicle group, indicating that OA inhibited tumor growth in mice in a dose-dependent manner. At the same time, no side effects were observed in the mice treated with OA, and all of the animals survived the experiment.

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