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Anti-cancer Effects of Novel Doxorubicin Prodrug PDOX in MCF-7 Breast Cancer Cells

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Specialty General Medicine
Date 2014 Aug 20
PMID 25135721
Citations 2
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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.

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References
1.
Bang Y, Van Cutsem E, Feyereislova A, Chung H, Shen L, Sawaki A . Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376(9742):687-97. DOI: 10.1016/S0140-6736(10)61121-X. View

2.
Wang Q, Zhong Y, Yuan J, Shao L, Zhang J, Tang L . Targeting therapy of hepatocellular carcinoma with doxorubicin prodrug PDOX increases anti-metastatic effect and reduces toxicity: a preclinical study. J Transl Med. 2013; 11:192. PMC: 3765954. DOI: 10.1186/1479-5876-11-192. View

3.
Schmid B, Chung D, Warnecke A, Fichtner I, Kratz F . Albumin-binding prodrugs of camptothecin and doxorubicin with an Ala-Leu-Ala-Leu-linker that are cleaved by cathepsin B: synthesis and antitumor efficacy. Bioconjug Chem. 2007; 18(3):702-16. DOI: 10.1021/bc0602735. View

4.
Groner B, Weiss A . Targeting survivin in cancer: novel drug development approaches. BioDrugs. 2013; 28(1):27-39. PMC: 3929033. DOI: 10.1007/s40259-013-0058-x. View

5.
Meyer H, Wilke H . Treatment strategies in gastric cancer. Dtsch Arztebl Int. 2011; 108(41):698-705. PMC: 3221435. DOI: 10.3238/arztebl.2011.0698. View