title: Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells.
abstract: Ursolic acid (3-hydroxy-urs-12-en-28-oic acid) is a pentacyclic triterpenoid derived from leaves, berries, fruits, and flowers of medicinal plants, such as Rosemarinus officinalis. Ursolic acid has been shown to inhibit tumorigenesis, tumor promotion, and suppress angiogenesis. In our present study, we found that ursolic acid decreased cell proliferation rate and induce apoptosis in human breast cancer cell line, MDA-MB-231. When we checked the expression levels of proteins associated with apoptosis signal by using immunoblotting, we found that ursolic acid induces various apoptotic molecules related to either extrinsic or intrinsic apoptosis signal pathway in MDA-MB-231 cells. In our study, we found that ursolic acid induced the appearance of Fas receptor and cleavage of caspase-8, -3 and PARP. We also found that ursolic acid induced Bax up-regulation and Bcl-2 down-regulation and release of cytochrome C to the cytosol from mitochondria. Moreover, ursolic acid cleaved caspase-9 and decreased mitochondrial membrane potential (ΔΨm) as shown with JC-1 staining. These data indicate that ursolic acid induce apoptosis through both mitochondrial death pathway and extrinsic death receptor dependent pathway in MDA-MB-231 cells. Our data clearly indicate that ursolic acid could be used as a potential anticancer drug for breast cancer.
authors: Laboratory of Clinical Biology and Pharmacogenomics and Center for Clinical Research and Genomics, Kyung Hee University, Seoul 130-701, Korea.
authors: Kyung Hun
authors: KH
authors: Kim
authors: Hye Sook
authors: HS
authors: Seo
authors: Han Seok
authors: HS
authors: Choi
authors: InHwa
authors: I
authors: Choi
authors: Yong Cheol
authors: YC
authors: Shin
authors: Seong-Gyu
authors: SG
authors: Ko
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014315:Triterpenes / Q000494:pharmacology*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000097245:Ursolic Acid
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000972:Antineoplastic Agents, Phytogenic; D020169:Caspases; D015853:Cysteine Proteinase Inhibitors; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053218:Receptors, Death Domain; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; D000097245:Ursolic Acid; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone