Skip to main content
Article
A Texaphyrin-oxaliplatin Conjugate that Overcomes both Pharmacologic and Molecular Mechanisms of Cisplatin Resistance in Cancer Cells
MedChemComm (2012)
  • Jonathan Arambula, The University of Texas at Austin
  • Jonathan L. Sessler, The University of Texas at Austin
  • Zahid H. Siddik, The University of Texas M. D. Anderson Cancer Center
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.
Keywords
  • Chemistry,
  • Texaphyrin,
  • Biochemistry,
  • oxaliTEX
Disciplines
Publication Date
September 26, 2012
DOI
10.1039/C2MD20206A
Citation Information
Jonathan Arambula, Jonathan L. Sessler and Zahid H. Siddik. "A Texaphyrin-oxaliplatin Conjugate that Overcomes both Pharmacologic and Molecular Mechanisms of Cisplatin Resistance in Cancer Cells" MedChemComm Vol. 3 Iss. 10 (2012) p. 1275 - 1281
Available at: http://works.bepress.com/jonathan-arambula/5/