Reversal of anticancer drug resistance by COTC based on intracellular glutathione and glyoxalase I

Daisuke Kamiya; Yuki Uchihata; Eiko Ichikawa; Kuniki Kato; Kazuo Umezawa

doi:10.1016/j.bmcl.2004.12.031

Reversal of anticancer drug resistance by COTC based on intracellular glutathione and glyoxalase I

Bioorg Med Chem Lett. 2005 Feb 15;15(4):1111-4. doi: 10.1016/j.bmcl.2004.12.031.

Authors

Daisuke Kamiya¹, Yuki Uchihata, Eiko Ichikawa, Kuniki Kato, Kazuo Umezawa

Affiliation

¹ Graduate School of Science and Technology, Keio University, Hiyoshi, Yokohama 223-8522, Japan.

PMID: 15686923
DOI: 10.1016/j.bmcl.2004.12.031

Abstract

Suppression of resistance to anticancer drugs by COTC of glyoxalase I (GloI) inhibitor targeting intracellular glutathione (GSH) and GloI was studied. Depletion of the cellular GSH content and inhibition of GloI by COTC increased chemotherapy-mediated apoptosis in apoptosis-resistant pancreatic adenocarcinoma AsPC-1 cells.

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Cell Line, Tumor
Cyclohexanones / chemistry*
Cyclohexanones / pharmacology
Drug Resistance, Neoplasm / drug effects*
Glutathione / antagonists & inhibitors*
Humans
Lactoylglutathione Lyase / antagonists & inhibitors*
Pancreatic Neoplasms / pathology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Cyclohexanones
2-crotonyloxymethyl-(4R,5R,6R)-4,5,6-trihydroxycyclohex- 2-enone
Lactoylglutathione Lyase
Glutathione