rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistancerhodacyanine导数癌细胞选择性地目标,克服了三苯氧胺耐药性.pdfVIP

Rhodacyanine Derivative Selectively Targets Cancer Cells and Overcomes Tamoxifen Resistance 1 2 1 1 1 3 John Koren III , Yoshinari Miyata , Janine Kiray , John C. O’Leary III , Lana Nguyen , Jianping Guo , 1 2 4 3 2 1 Laura J. Blair , Xiokai Li , Umesh K. Jinwal , Jin Q. Cheng , Jason E. Gestwicki , Chad A. Dickey * 1 Department of Molecular Medicine, USF Health Byrd Alzheimer’s Institute, College of Medicine, University of South Florida, Tampa, Florida, United States of America, 2 Departments of Pathology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America, 3 Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America, 4 College of Pharmacy, University of South Florida, Tampa, Florida, United States of America Abstract MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt