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Issue 10, 2012
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A texaphyrin–oxaliplatin conjugate that overcomes both pharmacologic and molecular mechanisms of cisplatin resistance in cancer cells

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Abstract

A texaphyrin–oxaliplatin conjugate, oxaliTEX, was designed to test the concept that a platinum analog can overcome defects in drug accumulation and p53-dependent DNA damage response in a tumor model expressing multifactorial mechanisms of cisplatin resistance. Cytotoxic studies resulted in a resistance factor of only 1.2, which essentially indicated complete reversal of resistance in 2780CP cells expressing a factor of 22 with cisplatin. Unlike cisplatin, oxaliTEX accumulated and formed DNA adducts, stabilized and activated p53 at similar levels in both sensitive and resistant cells, and induced apoptosis in both models. The ability and importance of a designer drug, such as oxaliTEX, to overcome cisplatin resistance by targeting two dominant resistance mechanisms is discussed.

Graphical abstract: A texaphyrin–oxaliplatin conjugate that overcomes both pharmacologic and molecular mechanisms of cisplatin resistance in cancer cells

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Publication details

The article was received on 31 May 2012, accepted on 16 Aug 2012 and first published on 21 Aug 2012


Article type: Concise Article
DOI: 10.1039/C2MD20206A
Citation: Med. Chem. Commun., 2012,3, 1275-1281
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    A texaphyrin–oxaliplatin conjugate that overcomes both pharmacologic and molecular mechanisms of cisplatin resistance in cancer cells

    J. F. Arambula, J. L. Sessler and Z. H. Siddik, Med. Chem. Commun., 2012, 3, 1275
    DOI: 10.1039/C2MD20206A

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