Top

Research Article

Split Viewer

Mol. Cells 2012; 34(1): 61-69

Published online May 23, 2012

https://doi.org/10.1007/s10059-012-0087-1

© The Korean Society for Molecular and Cellular Biology

Protein Kinase Cα Protects Against Multidrug Resistance in Human Colon Cancer Cells

Se-Kyoung Lee, Adeeb Shehzad, Jae-Chang Jung1, Jong-Kyung Sonn1, Jae-Tae Lee2, Jeen-Woo Park, and Young-Sup Lee*

School of Life Sciences, Kyungpook National University, Daegu 702-701, Korea, 1Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea, 2Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 700-721, Korea

Correspondence to : *Correspondence: yselee@knu.ac.kr

Received: March 21, 2012; Revised: April 26, 2012; Accepted: April 27, 2012

Abstract

Multidrug resistance is the phenomenon by which, after exposure to a single chemotherapeutic agent, cancer cells evade the agent’s cytotoxic effects as well as become resistant to several classes of diverse drugs. ATP-binding cassette (ABC) transporters are a family of transporter proteins that contribute to drug resistance via an ATP-dependent drug efflux pump. P-glycoprotein (P-gp) is a prominent ABC superfamily protein encoded by the mdr gene which has the ability to mediate the cellular extrusion of xenobiotics and anticancer drugs from tumor cells. Exclusively expressed P-gp cells from the human colon cancer HCT15/DOX line showed resistance to doxorubicin while parental HCT15 cells treated with doxorubicin displayed typical signs of apoptosis. In order to verify the hypothesis that expression of MDR is controlled in part, by protein kinase C (PKC), expression patterns of different PKC isoforms were examined in both cell lines. Of the PKC isoforms evaluated, the membrane translocation and expression levels of PKC? were strikingly increased in HCT15/ DOX cells. PKC? reversed doxorubicin-induced apoptosis through the scavenging of ROS as well as inhibition of PARP cleavage. In addition, inhibition of PKC? with Go6976, a specific inhibitor of classical PKC, led to re-duced MDR expression and increased doxorubicin-induced apoptosis. Knockdown of PKC? by siRNA diminished the protective effects of PKC? for doxorubicin-induced apoptosis. These results suggested that over-expression and activity of PKC? is closely as-sociated with the regulation of the MDR phenotype in human colon cancer HCT15 cells and provided insight into a new strategy for inhibiting doxorubicin resistance in human cancers.

Keywords apoptosis, doxorubicin, multidrug resistance, PKC alpha?

Article

Research Article

Mol. Cells 2012; 34(1): 61-69

Published online July 31, 2012 https://doi.org/10.1007/s10059-012-0087-1

Copyright © The Korean Society for Molecular and Cellular Biology.

Protein Kinase Cα Protects Against Multidrug Resistance in Human Colon Cancer Cells

Se-Kyoung Lee, Adeeb Shehzad, Jae-Chang Jung1, Jong-Kyung Sonn1, Jae-Tae Lee2, Jeen-Woo Park, and Young-Sup Lee*

School of Life Sciences, Kyungpook National University, Daegu 702-701, Korea, 1Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea, 2Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 700-721, Korea

Correspondence to:*Correspondence: yselee@knu.ac.kr

Received: March 21, 2012; Revised: April 26, 2012; Accepted: April 27, 2012

Abstract

Multidrug resistance is the phenomenon by which, after exposure to a single chemotherapeutic agent, cancer cells evade the agent’s cytotoxic effects as well as become resistant to several classes of diverse drugs. ATP-binding cassette (ABC) transporters are a family of transporter proteins that contribute to drug resistance via an ATP-dependent drug efflux pump. P-glycoprotein (P-gp) is a prominent ABC superfamily protein encoded by the mdr gene which has the ability to mediate the cellular extrusion of xenobiotics and anticancer drugs from tumor cells. Exclusively expressed P-gp cells from the human colon cancer HCT15/DOX line showed resistance to doxorubicin while parental HCT15 cells treated with doxorubicin displayed typical signs of apoptosis. In order to verify the hypothesis that expression of MDR is controlled in part, by protein kinase C (PKC), expression patterns of different PKC isoforms were examined in both cell lines. Of the PKC isoforms evaluated, the membrane translocation and expression levels of PKC? were strikingly increased in HCT15/ DOX cells. PKC? reversed doxorubicin-induced apoptosis through the scavenging of ROS as well as inhibition of PARP cleavage. In addition, inhibition of PKC? with Go6976, a specific inhibitor of classical PKC, led to re-duced MDR expression and increased doxorubicin-induced apoptosis. Knockdown of PKC? by siRNA diminished the protective effects of PKC? for doxorubicin-induced apoptosis. These results suggested that over-expression and activity of PKC? is closely as-sociated with the regulation of the MDR phenotype in human colon cancer HCT15 cells and provided insight into a new strategy for inhibiting doxorubicin resistance in human cancers.

Keywords: apoptosis, doxorubicin, multidrug resistance, PKC alpha?

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

Share this article on

  • line
  • mail

Related articles in Mol. Cells

Molecules and Cells

eISSN 0219-1032
qr-code Download