Anti-cancer effects of novel doxorubicin prodrug PDOX in MCF-7 breast cancer cells

被引：7
作者：
Zhang, Jue [1 ]
He, Liang [1 ]
Geng, Xia-fei [1 ]
Firestone, Raymond A. [2 ]
Hong, Ya-ping [2 ]
Li, Yan [1 ,3 ,4 ]
机构：
[1] Wuhan Univ, Zhongnan Hosp, Dept Oncol, Wuhan 430071, Peoples R China
[2] Nanjing Meihua Pharmaceut Ltd, Nanjing 210009, Jiangsu, Peoples R China
[3] Hubei Key Lab Tumor Biol Behav, Wuhan 430071, Peoples R China
[4] Hubei Canc Clin Study Ctr, Wuhan 430071, Peoples R China
来源：
JOURNAL OF HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY-MEDICAL SCIENCES | 2014年 / 34卷 / 04期
关键词：
breast cancer; doxorubicin; prodrug; molecular targeted therapy; cathepsin B; SENSITIVE DIPEPTIDE PRODRUGS; CATHEPSIN-B; PHASE-I; APOPTOSIS; METASTASIS; MECHANISMS; CARCINOMA; TOXICITY; RELEASE; PATHWAY;
D O I：
10.1007/s11596-014-1309-x
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 mu mol/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 G(1)/G(2) phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells.
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收藏
页码：521 / 528
页数：8
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