title: 2α-Hydroxyursolic Acid Inhibited Cell Proliferation and Induced Apoptosis in MDA-MB-231 Human Breast Cancer Cells through the p38/MAPK Signal Transduction Pathway.
abstract: The mechanisms of action of 2α-hydroxyursolic acid in inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 human breast cancer cells were investigated. The antiproliferative activity and cytotoxicity were determined by the methylene blue assay. The expression of proteins was determined using Western blot. 2α-Hydroxyursolic acid significantly inhibited MDA-MB-231 cell proliferation, and no cytotoxicity was observed at concentrations below 30 μM. 2α-Hydroxyursolic acid significantly down-regulated expressions of TRAF2, PCNA, cyclin D1, and CDK4 and up-regulated the expressions of p-ASK1, p-p38, p-p53, and p-21. 2α-Hydroxyursolic acid induced apoptosis in MDA-MB-231 cells by significantly increasing the Bax/Bcl-2 ratio and inducing the cleaved caspase-3. Additionally, treatment of SB203580, a p38 MAPK specific inhibitor, reversed the inhibition of PCNA, cyclin D1, and Bcl-2 expression induced by 2α-hydroxyursolic acid in MDA-MB-231 cells. These results suggested that 2α-hydroxyursolic acid exhibited anticancer activity through the inhibition of cell proliferation and the induction of apoptosis by regulating the p38/MAPK signal transduction pathway.
authors.affiliation: Department of Food Science, 245 Stocking Hall, Cornell University , Ithaca, New York 14853-7201, United States.
authors.forename: Xue
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Food Science, 245 Stocking Hall, Cornell University , Ithaca, New York 14853-7201, United States.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Food Science, 245 Stocking Hall, Cornell University , Ithaca, New York 14853-7201, United States.|Institute of Comparative and Environmental Toxicology, Cornell University , Ithaca, New York 14853-7201, United States.
authors.forename: Rui Hai
authors.initials: RH
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C412810:2-hydroxyursolic acid; C530104:CCND1 protein, human; D014315:Triterpenes; D019938:Cyclin D1; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: 2α-hydroxyursolic acid; apoptosis; breast cancer; cell proliferation; diet and cancer; phytochemicals