Physalis angulata induced G2/M phase arrest in human breast cancer cells.
Physalis angulata (PA) is employed in herbal medicine around the world. It is used to treat diabetes, hepatitis, asthma and malaria in Taiwan. We have evaluated PA as a cancer chemopreventive agent in vitro by studying the role of PA in regulation of proliferation, cell cycle and apoptosis in human breast cancer cell lines. PA inhibited cell proliferation and induced G2/M arrest and apoptosis in human breast cancer MAD-MB 231 and MCF-7 cell lines. In this study, under treatment with various concentrations of PA in MDA-MB 231 cell line, we checked mRNA levels for cyclin A and cyclin B1 and the protein levels of cyclin A and cyclin B1, Cdc2 (cyclin-dependent kinases), p21(waf1/cip1) and P27(Kip1) (cyclin-dependent kinase inhibitors), Cdc25C, Chk2 and Wee1 kinase (cyclin-dependent kinase relative factors) in cell cycle G2/M phase. From those results, we determined that PA arrests MDA-MB 231 cells at the G2/M phase by (i) inhibiting synthesis or stability of mRNA and their downstream protein levels of cyclin A and cyclin B1, (ii) increasing p21(waf1/cip1) and P27(kip1) levels, (iii) increasing Chk2, thus causing an increase in Cdc25C phosphorylation/inactivation and inducing a decrease in Cdc2 levels and an increase in Wee1 level. According to the results obtained, PA appears to possess anticarcinogenic properties; these results suggest that the effect of PA on the levels of phosphorylated/inactivated Cdc25C are mediated by Chk2 activation, at least in part, via p21(waf1/cip1) and P27(kip1) cyclin-dependent kinase inhibitors pathway to arrest cells at G2/M phase in breast cancer carcinoma cells.
Hsieh
Wen-Tsong
WT
Department of Pharmacology, China Medical University, 91 Hsueh-Shih Road, Taichung 404, Taiwan, ROC.
Huang
Kuan-Yuh
KY
Lin
Hui-Yi
HY
Chung
Jing-Gung
JG
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D019925:Cyclin A / Q000096:biosynthesis; D056750:Cyclin A1; D019926:Cyclin B / Q000096:biosynthesis; D056744:Cyclin B1; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis; D032321:Physalis / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020687:cdc25 Phosphatases / Q000096:biosynthesis
D000972:Antineoplastic Agents, Phytogenic; C503745:CCNA1 protein, human; C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019925:Cyclin A; D056750:Cyclin A1; D019926:Cyclin B; D056744:Cyclin B1; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases