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
Sep 12, 1991·Biochemical Pharmacology·E BignonA Crastes de Paulet
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
Dec 15, 1986·Biochemical Pharmacology·K HorganR E Mansel
May 1, 1995·Annals of Surgical Oncology·R R PerryB Greaves
Jan 20, 1995·Journal of Medicinal Chemistry·I R HardcastleS Neidle
Nov 28, 1994·FEBS Letters·Z Kiss
Apr 4, 1994·FEBS Letters·K M ConricodeJ H Exton
Jun 15, 1993·Biochemical and Biophysical Research Communications·F ImamuraH Akedo
Mar 6, 1996·Journal of the National Cancer Institute·Y KangR R Perry
Feb 27, 1996·Cancer Letters·G MartinR Bergoc
Feb 23, 1996·The Journal of Biological Chemistry·W D SingerP C Sternweis
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
Mar 26, 1998·Biochemical Pharmacology·A L ChengD S Chen
Aug 1, 1998·The Journal of Biological Chemistry·J A HessJ 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
Jan 5, 2000·Cell Proliferation·P E Budtz
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
Sep 19, 2002·Molecular Pharmacology·Susanne F Eisen, H Alex Brown
Aug 1, 1959·Canadian Journal of Biochemistry and Physiology·E G BLIGH, W J DYER
Citations
Jul 13, 2013·Veterinary Research Communications·J SarmientoG Morán
Oct 2, 2013·Hormones & Cancer·Nofrat SchwartzBarbara D Boyan
Jan 24, 2016·The International Journal of Neuropsychopharmacology·Balaji Krishnan
Mar 4, 2006·Cancer Letters·Myung-Jin KimPil-Young Yun
Jul 6, 2014·Molecular Neurobiology·Shin-Young ParkJoong-Soo Han
Aug 16, 2016·Journal of Neuropathology and Experimental Neurology·Christopher D GrahamKevin A Roth
Oct 21, 2004·Anti-cancer Drugs·Oliver TreeckOlaf Ortmann
Feb 10, 2021·Cell & Bioscience·Hui-Ju TsaiChing-Ping Tseng