Protective Effect of PKC Affecting Taxol-induced Cytotoxicity in MCF-7 Cells.
- Author:
Jay Min OH
1
;
Kyung Min JUNG
;
Hyun Ju BANG
;
Hong Seob SO
;
Rae Kil PARK
;
Jeong Joong KIM
;
Min Kyu CHOI
;
Seung Taeck PARK
;
Yeun Tai CHUNG
Author Information
1. Department of Anatomy and 1Microbiology, School of Medicine, Wonkwang University, Iksan, Korea.
- Publication Type:Original Article
- Keywords:
Paclitaxel (taxol);
Protein kinase C (PKC);
Toxol-indeucd apoptosis;
MCF-7 cells
- MeSH:
Apoptosis;
Breast;
Breast Neoplasms;
Caspases;
Cell Cycle;
Curcumin;
Cyclic AMP-Dependent Protein Kinases;
Humans;
MCF-7 Cells*;
Melanoma;
Myristic Acid;
Paclitaxel;
Protein Kinase C;
Signal Transduction;
Thapsigargin
- From:Korean Journal of Anatomy
2000;33(5):571-578
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Paclitaxel (taxol) is known as effective drug inhibition of cell cycle encouraging activity in human ovarian and metastatic breast cancers and malignant melanoma. It is an antimicrotubule agent that is believed to mediate its antineoplastic effects by inducing mitotic arrest followed by apoptosis. The relation between phorbol 12 myristate 13 acetate (PMA), protein kinase C (PKC) activator, and taxol-induced apoptosis is not well understood until now. This study was performed to investigate the effects of PMA on the signal transduction pathways of taxol-induced apoptosis in MCF-7 human breast carcinoma cells. Taxol-induced apoptosis is attenuated by curcumine, JNK inhibitor, and pyrrolidine dithiocarbamate (PDTC), inhibitor of NFkB. Pretreatment with PKC activator (PMA) or protein kinase A (PKA) activators (forskolin and dibutyryl cAMP) inhibited taxol-induced apoptosis in MCF-7 cells. In addition, thapsigargin, a specific inhibitor of endoplasmic reticulum(ER) Ca(2+)-ATPase and CaCl2, also blocked the activation of caspases by taxol. From these results suggest that taxol-induced apoptosis may be mediated via JNK or NFkB pathway and PKC activation.
