Paradoxical and contradictory effects of imatinib in two cell line models of hormone-refractory prostate cancer

The Prostate
Henrique J CardosoSílvia Socorro

Abstract

Imatinib mesylate is a chemotherapeutic drug that inhibits the tyrosine kinase activity of c-KIT and has been successfully used to treat leukemias and some solid tumors. However, its application for treatment of hormone-refractory prostate cancer (HRPC) has shown modest effectiveness and did not follow the outcomes in cultured cells or animal models. Moreover, the molecular pathways by which imatinib induces cytotoxicity in prostate cancer cells are poorly characterized. Two cell line models of HRPC (DU145 and PC3) were exposed to 20 μM of imatinib for 6-72 hr. MTS assay was used to assess cell viability during the course of experiment. Gene expression analysis of c-KIT, cell-cycle and apoptosis regulators, and angiogenic factors was determined by means of real-time PCR, western blot, and/or immunocytochemistry. The enzymatic activity of the apoptosis effector, caspase-3, was determined by a colorimetric assay. Imatinib significantly decreased the viability of DU145 cells but paradoxically augmented the viability of PC3 cells. DU145 cells displayed diminished expression of anti-apoptotic Bcl-2 protein and augmented levels of caspase-8 and -9, as well as, increased enzymatic activity of caspase-3 in response to imatinib. No diff...Continue Reading

References

May 1, 1979·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·I KeydarH J Brenner
Mar 15, 1978·International Journal of Cancer. Journal International Du Cancer·K R StoneD F Paulson
Jan 1, 1991·Journal of Surgical Oncology·S J RubinR R Weichselbaum
Dec 20, 1990·The Journal of Steroid Biochemistry and Molecular Biology·J TrapmanA O Brinkmann
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·J M JürgensmeierJ C Reed
Jul 4, 1998·Molecular Cell·S M SrinivasulaE S Alnemri
Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
Jul 12, 2002·Cancer Chemotherapy and Pharmacology·A MunshiR E Meyn
Aug 16, 2002·The New England Journal of Medicine·George D DemetriHeikki Joensuu
Jan 8, 2004·Journal of the National Cancer Institute·Kiichiro BeppuCarol J Thiele
Mar 23, 2004·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Jana Knillová, Zdenek Kolár
Mar 25, 2004·The American Journal of Pathology·Maria Paola ParonettoClaudio Sette
May 11, 2004·Cancer Chemotherapy and Pharmacology·Zariana NikolovaRenaud Capdeville
Aug 18, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paul MathewChristopher Logothetis
Oct 8, 2004·The New England Journal of Medicine·Daniel P PetrylakE David Crawford
Nov 19, 2004·Neoplasia : an International Journal for Oncology Research·Matthias D HoferMark A Rubin
May 14, 2005·CA: a Cancer Journal for Clinicians·Irene M GhobrialAlex A Adjei
Jun 17, 2005·Cancer Research·Wai Kei KwokXianghong Wang
Jul 5, 2005·Comptes rendus biologies·Safa Lucken-Ardjomande, Jean-Claude Martinou
Aug 27, 2005·Clinical Pharmacokinetics·Bin PengHorst Schran
Oct 11, 2005·Journal of Cellular Biochemistry·Shaun McKenzie, Natasha Kyprianou
Dec 1, 2005·Molecular Cancer Research : MCR·Cécile-Marie Aliouat-DenisJorge E Vialard
May 16, 2006·Apoptosis : an International Journal on Programmed Cell Death·K O'ConnorR W G Watson
Nov 8, 2007·Cancer Biology & Therapy·Yu KimuraJanina Baranowska-Kortylewicz
Nov 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John C McAuliffeJonathan C Trent
Dec 22, 2007·Nature Reviews. Molecular Cell Biology·Richard J Youle, Andreas Strasser
Jan 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Dominik R BertholdIan F Tannock
Mar 4, 2008·Trends in Cell Biology·Jerry E Chipuk, Douglas R Green
Aug 21, 2008·Neoplasia : an International Journal for Oncology Research·Christoph WiesnerR Daniel Bonfil

❮ Previous
Next ❯

Citations

Nov 19, 2015·International Journal of Molecular Sciences·Ewa MajJoanna Wietrzyk
Feb 7, 2018·Scientific Reports·Mehdi JorfiDaniel Irimia
Jul 26, 2019·Molecular Biology Reports·Sercan ErgünÜmmet Abur
Jun 29, 2017·Journal of Cell Communication and Signaling·Henrique J CardosoSílvia Socorro
Jan 18, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Alaa E El-SisiSally E Abu-Risha
Apr 13, 2021·Archives of Biochemistry and Biophysics·Heba H MansourMervat M Omran

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

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