title: Gambogic acid promotes apoptosis and resistance to metastatic potential in MDA-MB-231 human breast carcinoma cells.
abstract: Gambogic acid (GA) is considered a potent anti-tumor agent for its multiple effects on cancer cells in vitro and in vivo. Low concentrations of GA (0.3-1.2 µmol/L) can suppress invasion of human breast carcinoma cells without affecting cell viability. To get a whole profile of the inhibition on breast cancers, higher concentrations of GA and spontaneous metastatic animal models were employed. Treatment with GA (3 and 6 µmol/L) induced apoptosis in MDA-MB-231 cells and the accumulation of reactive oxygen species (ROS). Furthermore, GA induced PARP cleavage, activation of caspase-3, caspase-8, and caspase-9, as well as an increased ratio of Bax/Bcl-2. Moreover, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome c (Cyt c) from mitochondria were observed, indicating that GA induced apoptosis through accumulation of ROS and mitochondrial apoptotic pathway. GA also inhibited cell survival via blocking Akt/mTOR signaling. In vivo, GA significantly inhibited the xenograft tumor growth and lung metastases in athymic BALB/c nude mice bearing MDA-MB-231 cells. Collectively, these data provide further support for the multiple effects of GA on human breast cancer cells, as well as for its potential application to inhibit tumor growth and prevent metastasis in human cancers.
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Qi
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Qinsheng
authors.initials: Q
authors.lastname: Dai
authors.forename: Fanni
authors.initials: F
authors.lastname: Li
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Wang
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D044004:Xanthones / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D017382:Reactive Oxygen Species; D044004:Xanthones; D051028:bcl-2-Associated X Protein; C052659:gambogic acid; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9