Anti-cancer effects of novel doxorubicin prodrug PDOX in MCF-7 breast cancer cells.
10.1007/s11596-014-1309-x
- Author:
Jue ZHANG
1
;
Liang HE
;
Xia-fei GENG
;
Raymond A FIRESTONE
;
Ya-ping HONG
;
Yan LI
Author Information
1. Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China, zhangjue_123@163.com.
- Publication Type:Journal Article
- MeSH:
Antibiotics, Antineoplastic;
pharmacology;
Breast Neoplasms;
drug therapy;
metabolism;
pathology;
Caspase 3;
metabolism;
Cell Line, Tumor;
Cyclin-Dependent Kinase Inhibitor p21;
biosynthesis;
Doxorubicin;
analogs & derivatives;
pharmacology;
Drug Screening Assays, Antitumor;
methods;
Female;
G1 Phase;
drug effects;
G2 Phase;
drug effects;
Gene Expression Regulation, Neoplastic;
drug effects;
Humans;
Oligopeptides;
pharmacology;
Signal Transduction;
drug effects;
Tumor Suppressor Protein p53;
biosynthesis
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2014;34(4):521-528
- CountryChina
- Language:English
-
Abstract:
Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. This study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21 signaling alterations were studied. Abundant cathepsin B was found in the MCF-7 cells, and treatment with PDOX and DOX triggered dose- and time-dependent cytotoxicity and resulted in a significant reduction in cell viability. The IC50 of PDOX and DOX was 3.91 and 0.94 μmol/L, respectively. Both PDOX and DOX caused an up-regulation of the P53/P21-related signal pathway, and PDOX significantly increased expression of P53 and caspase 3, and arrested the cell cycle at the G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells.
