title: Pculin02H, a curcumin derivative, inhibits proliferation and clinical drug resistance of HER2-overexpressing cancer cells.
abstract: Amplification of the HER2 gene (also known as neu or ErbB2) or overexpression of HER2 protein has become a solicitous therapeutic target in metastatic and clinical drug-resistance cancer. In our present work, a new series of curcumin derivatives were designed and synthesized using curcumin as model. Here, we evaluated whether curcumin derivatives have better efficiency to degrade HER2 than curcumin. Among these test compounds, pculin02H had better efficiency to inhibit the expression of HER2 than curcumin. Moreover, pculin02H preferentially suppressed the growth of HER2-overexpressing cancer cell lines. Pculin02H induced G2/M cell cycle arrest followed by apoptosis. Interestingly, our results suggested that a posttranslational mechanism contributed to pculin02H-induced HER2 depletion in HER2-overexpressing cancer cells. We found that pculin02H significantly enhanced the antitumor efficacy of clinical drugs on HER2-overexpressing cancer cells as well as efficiently reduced HER2-induced drug resistance. These findings may provide an alternative preventive or therapeutic strategy against HER2-overexpressing cancer cells.
authors: School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors: Jin-Cherng
authors: JC
authors: Lien
authors: Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine, I-Shou University, Kaohsiung, Taiwan.
authors: Chao-Ming
authors: CM
authors: Hung
authors: Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan.
authors: Yi-Jing
authors: YJ
authors: Lin
authors: School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors: Hui-Chang
authors: HC
authors: Lin
authors: Department of Pharmacy, Mackay Memorial Hospital, Hsinchu, Taiwan.
authors: Ting-Chia
authors: TC
authors: Ko
authors: Department of Counseling Psychology, Toko University, Chiayi, Taiwan.
authors: Li-Chung
authors: LC
authors: Tseng
authors: School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors: Sheng-Chu
authors: SC
authors: Kuo
authors: Department of Food Science, Rutgers University, New Brunswick, NJ, USA.
authors: Chi-Tang
authors: CT
authors: Ho
authors: School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan. Electronic address: leejh@mail.cmu.edu.tw.
authors: Jang-Chang
authors: JC
authors: Lee
authors: Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan; Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan; Department of Health and Nutrition Biotechnology, College of Health Science, Asia University, Taichung, Taiwan. Electronic address: tdway@mail.cmu.edu.tw.
authors: Tzong-Der
authors: TD
authors: Way
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D003474:Curcumin / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects* / Q000235:genetics; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D003474:Curcumin; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: Apoptosis; G2/M arrest; HER2; Pculin02H