title: p53 is a key regulator for osthole-triggered cancer pathogenesis.
abstract: Osthole has been reported to have antitumor activities via the induction of apoptosis and inhibition of cancer cell growth and metastasis. However, the detailed molecular mechanisms underlying the anticancer effects of osthole in human colon cancer remain unclear. In the present study, we have assessed osthole-induced cell death in two different human colon cancer cell lines, HCT116 and SW480. Our results also showed that osthole activated proapoptotic signaling pathways in human colon cancer cells. By using cell culture insert system, osthole reduced cell motility in both human colon cancer cell lines. This study also provides evidence supporting the potential of osthole in p53 activation. Expression of p53, an apoptotic protein, was remarkably upregulated in cells treated with osthole. Importantly, the levels of phosphorylation of p53 on Ser15 (p-p53) and acetylation of p53 on Lys379 (acetyl-p53) were increased under osthole treatment. Our results also demonstrated that p53 was activated followed by generation of reactive oxygen species (ROS) and activation of c-Jun N-terminal kinase (JNK). Our study provides novel insights of p53-mediated responses under osthole treatment. Taken together, we concluded that osthole induces cancer cell death and inhibits migratory activity in a controlled manner and is a promising candidate for antitumor drug development.
authors.affiliation: Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 402, Taiwan ; Preventive Medicine Center, Department of Community Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan ; Division of Colon and Rectal Surgery, Department of Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan ; School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
authors.forename: Ssu-Ming
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Department of Biotechnology, Asia University, Taichung 413, Taiwan.
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Tsai
authors.affiliation: Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua 500, Taiwan.
authors.forename: Dar-Ren
authors.identifier: 0000-0002-0897-4374
authors.initials: DR
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Min-Ying
authors.initials: MY
authors.lastname: Wang
authors.affiliation: Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua 500, Taiwan.
authors.forename: Wei-Lan
authors.identifier: 0000-0003-4398-7610
authors.initials: WL
authors.lastname: Yeh
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003374:Coumarins / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D003374:Coumarins; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048670:MAP Kinase Kinase 4; C046627:osthol