Bcr-Abl-independent Mechanism of Resistance to Imatinib in K562 Cells: Induction of Cyclooxygenase-2 (COX-2) by Histone Deacetylases (HDACs)

Overview

Journal Leuk Res

Date 2010 Mar 9

PMID 20206383

Citations 10

Authors

Arunasree M Kalle

Sachchidanand Sachchidanand

Reddanna Pallu

Affiliations

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Abstract

Our previous studies have shown that overexpression of MDR1 and cyclooygenase-2 (COX-2) resulted in resistance development to imatinib in chronic myelogenous leukemia (CML) K562 (IR-K562) cells. In the present study, the regulatory mechanism of MDR1 induction by COX-2 was investigated. A gradual overexpression of MDR1 and COX-2 during the process of development was observed. Furthermore, down regulation of MDR1 upon COX-2 knockdown by siRNA showed a decrease in the PKC levels and activation of PKC by addition of PGE(2) to K562 cells, suggesting a role for PKC in the COX-2 mediated induction of MDR1. The present study demonstrates COX-2 induction by HDACs and MDR1 induction by COX-2 via PGE(2)-cAMP-PKC-mediated pathway.

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