Phospholipase C-protein kinase C mediated phospholipase D activation pathway is involved in tamoxifen induced apoptosis

Journal of Cellular Biochemistry
Soo-Jung AhnDong-Young Noh

Abstract

Tamoxifen (TAM) is the endocrine therapeutic agent the most widely used in the treatment of breast cancer, and it operates primarily through the induction of apoptosis. In this study, we attempted to elucidate the non-ER mediated mechanism behind TAM treatment, involving the phospholipase C-protein kinase C (PLC-PKC) mediated phospholipase D (PLD) activation pathway, using multimodality methods. In TAM treated MCF7 cells, the PLC and PLD protein and mRNA levels increased. Phosphatidylethanol (PEt) and diacylglycerol (DAG) generation also increased, showing increased activity of PLD and PLCgamma1. Translocation of PKCalpha, from cytosol to membrane, was observed in TAM treated cells. By showing that both PKC and PLC inhibitors could reduce the effects of TAM-induced PLD activation, we confirmed the role of PKC and PLC as upstream regulators of PLD. Finally, we demonstrated that TAM treatment reduced the viability of MCF7 cells and brought about rapid cell death. From these results, we confirmed the hypothesis that TAM induces apoptosis in breast cancer cells, and that the signal transduction pathway, involving PLD, PLC, and PKC, constitutes one of the possible mechanisms underlying the non-ER mediated effects associated with TAM.

References

Jan 1, 1990·Progress in Lipid Research·Z Kiss
Jul 31, 1989·Biochemical and Biophysical Research Communications·S C KinskyS H Benedict
Dec 21, 1988·Journal of the National Cancer Institute·C A O'BrianB W Anderson
Sep 11, 1986·Nature·W H MoolenaarS W de Laat
Jan 20, 1995·Journal of Medicinal Chemistry·I R HardcastleS Neidle
Jun 15, 1993·Biochemical and Biophysical Research Communications·F ImamuraH Akedo
Mar 6, 1996·Journal of the National Cancer Institute·Y KangR R Perry
Jun 7, 1996·The Journal of Biological Chemistry·U GundimedaR Gopalakrishna
May 24, 1996·Chemistry and Physics of Lipids·Z Kiss
Mar 4, 1997·International Journal of Cancer. Journal International Du Cancer·M C CabotR C Jones
Aug 15, 1997·The Journal of Biological Chemistry·R DattaD Kufe
Apr 18, 1998·The Journal of Biological Chemistry·D S MinJ H Exton
Aug 26, 1998·International Journal of Cancer. Journal International Du Cancer·Y LavieM C Cabot
Dec 5, 1998·Biochimica Et Biophysica Acta·J H Exton
Apr 29, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·D A CameronW R Miller
Oct 12, 2001·Apoptosis : an International Journal on Programmed Cell Death·S Mandlekar, A N Kong
Aug 1, 1959·Canadian Journal of Biochemistry and Physiology·E G BLIGH, W J DYER

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Citations

Aug 16, 2016·Journal of Neuropathology and Experimental Neurology·Christopher D GrahamKevin A Roth

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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