Pculin02H, a curcumin derivative, inhibits proliferation and clinical drug resistance of HER2-overexpressing cancer cells. (25th June 2015)

• Record Type: Journal Article
• Authors: Lien, Jin-Cherng; Hung, Chao-Ming; Lin, Yi-Jing; Lin, Hui-Chang; Ko, Ting-Chia; Tseng, Li-Chung; Kuo, Sheng-Chu; Ho, Chi-Tang; Lee, Jang-Chang; Way, Tzong-Der
• Is Part Of: Chemico-biological interactions. Volume 235(2015)
• Page Start: 17
• Page End: 26
• Publication Date: 2015-06-25
• Subjects: CHX cycloheximide -- EGFR epithelial growth factor receptor -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- NSCLC non-small cell lung cancer -- PBS phosphate-buffered saline -- PI propidium iodide; HER2 -- Pculin02H -- G2/M arrest -- Apoptosis; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2015.04.005
• Languages: English
• ISSNs: 0009-2797

Abstract

Highlights: Pculin02H preferentially suppressed the growth of HER2-overexpressing cancer cells. Pculin02H induced G2/M cell cycle arrest followed by apoptosis. A posttranslational mechanism contributed to pculin02H-induced HER2 depletion. Pculin02H significantly enhanced the antitumor efficacy of clinical drugs on 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.