Protein phosphatase 2A inhibition and circumvention of cisplatin cross-resistance by novel TCM-platinum anticancer agents containing demethylcantharidin

被引：38

作者：

To, KKW

Wang, XN

Yu, CW

Ho, YP ^{[1
]}

Au-Yeung, SCF

机构：

[1] Chinese Univ Hong Kong, Fac Med, Sch Pharm, Hong Kong, Hong Kong, Peoples R China

[2] Chinese Univ Hong Kong, Fac Sci, Dept Chem, Hong Kong, Hong Kong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 17期

关键词：

demethylcantharidin; protein phosphatase inhibition; cisplatin resistance; nucleotide excision repair;

D O I：

10.1016/j.bmc.2004.07.009

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：

Novel TCM-platinum compounds [Pt(C8H8O5)(NH2R)(2)]1-5, derived from integrating demethylcantharidin, a modified component from a traditional Chinese medicine (TCM) with a platinum moiety, possess anticancer and protein phosphatase 2A inhibition properties. The compounds are able to circumvent cisplatin resistance by apparently targeting the DNA repair mechanism. Novel isosteric analogues [Pt(C9H10O4)(NH2R)(2)] A and B, devoid of PP2A-inhibitory activity, were found to suffer from an enhanced DNA repair and were cross-resistant to cisplatin. The results advocate a well-defined structure-activity requirement associating the PP2A-inhibiting demethylcantharidin with the circumvention of cisplatin cross-resistance demonstrated by TCM-Pt compounds 1-5. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：4565 / 4573

页数：9

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