期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 85, 期 -, 页码 498-507出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.08.006
关键词
Podophyllotoxin; Cytotoxicity; Apoptosis; Multidrug resistance; MDR-1
资金
- National S & T Major Special Project on Major New Drug Innovation [2011ZX09307-002-01, 2013ZX09508104]
- PUMC Youth Fund [33320140074]
- Fundamental Research Funds for the Central Universities
- Program for Innovative Research Team in IMPLAD [IT1305]
Cancer multidrug resistance (MDR) is a common cause of treatment failure in cancer patients. Increased expression of permeability glycoprotein (P-gp), which is also known as MDR-1, is the main cause of multidrug resistance. Podophyllotoxin derivatives hold great promise in the battle to overcome multidrug resistance, as they can induce cytotoxicity through multiple mechanisms. Here, we synthesized sixteen novel podophyllotoxin derivatives and evaluated their cytotoxicities in human cancer cell lines, HeLa, 1(562 and K562/A02. Some of these compounds were more potent than etoposide, a clinically relevant inhibitor of DNA repair enzymes. In particular, compound 5p exhibited the most potent activity toward drug-resistant K562/A02 cells, as it robustly inhibited tumor cell proliferation and induced apoptosis. Furthermore, preliminary investigation suggested that 5p inhibited the expression of MDR-1 in K562/A02 cells more effectively than etoposide. (C) 2014 Elsevier Masson SAS. All rights reserved.
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