title: Germacrone inhibits the proliferation of breast cancer cell lines by inducing cell cycle arrest and promoting apoptosis.
abstract: Traditional medicinal herbs are an untapped source of potential pharmaceutical compounds. This study aims to determine whether the proliferation of breast cancer cell lines could be inhibited by germacrone, a natural product isolated from Rhizoma curcuma. Germacrone treatment significantly inhibited cell proliferation, increased lactate dehydrogenase (LDH) release, and induced mitochondrial membrane potential (ΔΨm) depolarization in both MCF-7 and MDA-MB-231 cells in a dose-dependent manner. Germacrone induced MDA-MB-231 and MCF-7 cell cycle arrest at the G0/G1 and G2/M phases respectively and induced MDA-MB-231 cell apoptosis. Furthermore, germacrone treatment significantly increased Bok expression and cytochrome c release from mitochondria without affecting Bcl-2, Bcl-xL, Bax, and Bim protein expressions. In addition, germacrone treatment induced caspase-3, 7, 9, PARP cleavage. We concluded that germacrone inhibited the proliferation of breast cancer cell lines by inducing cell cycle arrest and apoptosis through mitochondria-mediated caspase pathway. These results might provide some molecular basis for the anti-tumor activity of Rhizoma curcuma.
authors.affiliation: Institute of Chinese Medical Sciences, University of Macau, Av. Padre Toma's Pereira S.J., Taipa, Macau, 999078, China.
authors.forename: Zhangfeng
authors.initials: Z
authors.lastname: Zhong
authors.forename: Xiuping
authors.initials: X
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Zengtao
authors.initials: Z
authors.lastname: Xu
authors.forename: Keyuan
authors.initials: K
authors.lastname: Zhou
authors.forename: Tie
authors.initials: T
authors.lastname: Wu
authors.forename: Liao
authors.initials: L
authors.lastname: Cui
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D045788:Sesquiterpenes, Germacrane / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D045788:Sesquiterpenes, Germacrane; C048393:germacrone; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D020169:Caspases