title: Decursin exerts anti-cancer activity in MDA-MB-231 breast cancer cells via inhibition of the Pin1 activity and enhancement of the Pin1/p53 association.
abstract: The peptidyl-prolyl cis/trans isomerase Pin1 is overexpressed in a wide variety of cancer cells and thus considered as an important target molecule for cancer therapy. This study demonstrates that decursin, a bioactive compound from Angelica gigas, exert the anti-cancer effect against breast cancer cells via regulation of Pin1 and its related signaling molecules. We observed that decursin induced G1 arrest with decrease in cyclin D1 level in Pin1-expressing breast cancer cells MDA-MB-231, but not Pin1-non-expressing breast cancer cells MDA-MB-157. In addition, decursin significantly reduced protein expression and enzymatic activity of Pin1 in MDA-MB-231 cells. Further, we found that decursin treatment enhanced the p53 expression level and failed to down-regulate Pin1 in the cells transfected with p53 siRNA, indicating the importance of p53 in the decursin-mediated Pin1 inhibition in MDA-MB-231 cells. Decursin stimulated association between Pin1 to p53. Moreover, decursin facilitated p53 transcription in MDA-MB-231 cells. Overall, our current study suggests the potential of decursin as an attractive cancer therapeutic agent for breast cancer by targeting Pin1 protein.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, South Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jung
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
mesh_terms: D029969:Angelica / Q000737:chemistry; D001578:Benzopyrans / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002087:Butyrates / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D001578:Benzopyrans; D002087:Butyrates; C530104:CCND1 protein, human; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C101278:decursin; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase
keywords: Pin1; anti-cancer; breast cancer; cell cycle; decursin; p53