T-Type Ca2+ Channel Inhibition Sensitizes Ovarian Cancer to Carboplatin

Molecular Cancer Therapeutics
Barbara DziegielewskaJill K Slack-Davis

Abstract

Ovarian cancer is the deadliest gynecologic cancer, due in large part to the diagnosis of advanced stage disease, the development of platinum resistance, and inadequate treatment alternatives. Recent studies by our group and others have shown that T-type calcium (Ca(2+)) channels play a reinforcing role in cancer cell proliferation, cell-cycle progression, and apoptosis evasion. Therefore, we investigated whether T-type Ca(2+) channels affect ovarian tumor growth and response to platinum agents. Inhibition of T-type Ca(2+) channels with mibefradil or by silencing expression resulted in growth suppression in ovarian cancer cells with a simultaneous increase in apoptosis, which was accompanied by decreased expression of the antiapoptotic gene survivin (BIRC5). Analysis of intracellular signaling revealed mibefradil reduced AKT phosphorylation, increased the levels and nuclear retention of FOXO transcription factors that repress BIRC5 expression, and decreased the expression of FOXM1, which promotes BIRC5 expression. Combining carboplatin with mibefradil synergistically increased apoptosis in vitro. Importantly, mibefradil rendered platinum-resistant ovarian tumors sensitive to carboplatin in a mouse model of peritoneal metastasis...Continue Reading

References

Jul 1, 1994·Circulation Research·S K Mishra, K Hermsmeyer
Oct 5, 2002·Cellular and Molecular Life Sciences : CMLS·N ZaffaroniM G Daidone
Dec 31, 2002·Physiological Reviews·Edward Perez-Reyes
Jun 17, 2003·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Cynthia CohenRobert Santoianni
Apr 6, 2006·The Journal of Biological Chemistry·Ningxi ZhuMuxiang Zhou
Jul 10, 2007·Cancer Research·Roland H StauberShirley K Knauer
Dec 18, 2007·Cell·David E Clapham
Aug 22, 2008·Trends in Cell Biology·Tobias B Dansen, Boudewijn M T Burgering
Feb 13, 2009·Molecular Biology of the Cell·Petra ObexerMichael Ausserlechner
May 28, 2009·Cancer Research·Minakshi GuhaDario C Altieri
Sep 1, 2009·Cell Cycle·Minakshi Guha, Dario C Altieri
Apr 17, 2010·International Journal of Radiation Oncology, Biology, Physics·Gianni CapalboFranz Rödel
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Jan 12, 2012·Current Oncology Reports·David N Church, Denis C Talbot
Mar 14, 2012·Cancer Letters·Dario C Altieri
Jun 12, 2012·Current Medicinal Chemistry·F RödelS Hehlgans
Jun 26, 2012·Nucleic Acids Research·Andreas UntergasserSteven G Rozen
Jul 24, 2012·The Journal of Biological Chemistry·Gregory R MonteithSarah J Roberts-Thomson
Jan 5, 2013·Biochemical Pharmacology·Nicholas C K ValerieJaroslaw Dziegielewski
Jan 30, 2013·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Lifeng ChenFeiyun Zheng
Jul 11, 2013·Nature Communications·Silvia DomckeNikolaus Schultz
Jul 17, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R J KellyG Giaccone
Aug 14, 2013·Archives of Biochemistry and Biophysics·Rita Nogueira-FerreiraTiago Henriques-Coelho
Nov 8, 2013·Molecular Biology Reports·Romain BoidotSarab Lizard-Nacol
Nov 14, 2013·Bioorganic & Medicinal Chemistry Letters·Sun Jeong JangJae Yeol Lee
Nov 23, 2013·Gynecologic Oncology·Roser MirPepita Giménez-Bonafé
Jan 7, 2015·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Jan 17, 2015·Seminars in Cell & Developmental Biology·Dario C Altieri

❮ Previous
Next ❯

Citations

Jan 17, 2019·American Journal of Physiology. Cell Physiology·Zhen ZhengSongwei Wu
Apr 8, 2017·Nature Reviews. Cancer·Gregory R MonteithSarah J Roberts-Thomson
Jan 27, 2019·Cancers·Lauren Antal, Miguel Martin-Caraballo
Mar 20, 2019·Cancers·Philippe KischelHalima Ouadid-Ahidouch
Aug 14, 2020·Cancers·Laura CaraviaSilviu Cristian Voinea
Feb 13, 2020·Cancers·Carla BarcelóAnna Macià
Dec 12, 2018·MAbs·Catherine J HutchingsTheodore G Clark
Sep 23, 2018·Breast Cancer Research and Treatment·Anamika Bhargava, Sumit Saha
Oct 27, 2020·Journal of Biomolecular Structure & Dynamics·Neema KumariSubha Narayan Rath
Jan 19, 2018·Cancer Research·Marta C SallánCarles Cantí
Jun 11, 2019·Gynecologic Oncology·Barbara N HardingNoel S Weiss
Oct 24, 2020·ACS Combinatorial Science·Milad AshrafizadehPooyan Makvandi
Apr 11, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Lía AlzaCarles Cantí
Jun 15, 2019·Cell Calcium·Sana KoubaMarie Potier-Cartereau
Jul 22, 2021·The FEBS Journal·Ling WuLiang Zhao
Jul 31, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jeong-Hun LeeKyung-Tae Lee

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

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

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.