Inhibition of store-operated channels by carboxyamidotriazole sensitizes ovarian carcinoma cells to anti-Bclx L  strategies through Mcl-1 down-regulation

Marie-Laure Bonnefond; Romane Florent; Sophie Lenoir; Bernard Lambert; Edwige Abeilard; Florence Giffard; Marie-Hélène Louis; Nicolas Elie; Mélanie Briand; Denis Vivien; Laurent Poulain; Pascal Gauduchon; Monique N’Diaye

doi:10.18632/oncotarget.26084

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

Inhibition of store-operated channels by carboxyamidotriazole sensitizes ovarian carcinoma cells to anti-Bclx_L strategies through Mcl-1 down-regulation

Marie-Laure Bonnefond, Romane Florent, Sophie Lenoir, Bernard Lambert, Edwige Abeilard, Florence Giffard, Marie-Hélène Louis, Nicolas Elie, Mélanie Briand, Denis Vivien, Laurent Poulain, Pascal Gauduchon and Monique N’Diaye _

PDF | HTML | Supplementary Files | How to cite

Oncotarget. 2018; 9:33896-33911. https://doi.org/10.18632/oncotarget.26084

Metrics: PDF 1419 views | HTML 1826 views | ?

Abstract

Marie-Laure Bonnefond1,2,*, Romane Florent1,2,*, Sophie Lenoir3, Bernard Lambert1,2,4, Edwige Abeilard1,2, Florence Giffard1,2, Marie-Hélène Louis1,2, Nicolas Elie1,5, Mélanie Briand1,2,6, Denis Vivien3, Laurent Poulain1,2, Pascal Gauduchon1,2 and Monique N’Diaye1,2

1Normandie University, UNICAEN, INSERM U1086 ANTICIPE, Interdisciplinary Research Unit for Cancer Prevention and Treatment, BioTICLA Axis, Biology and Innovative Therapeutics for Ovarian Cancers, Caen, France

2UNICANCER, François Baclesse Cancer Center, BioTICLA Laboratory, Caen, France

3Normandie University, UNICAEN, INSERM UMR-S 1237, Physiopathologie et Imagerie des Troubles Neurologiques (PhIND), tPA and Neurovascular Disorders Team, Caen, France

4Délégation Régionale de Normandie, CNRS, Caen, France

5Normandie University, UNICAEN, Centre de Microscopie Appliqué à la Biologie, CMabio3, Structure Fédérative 4206 ICORE, Caen, France

6Centre de Ressources Biologiques, OvaRessources, François Baclesse Cancer Center, Caen, France

*These authors have contributed equally to this work

Correspondence to:

Monique N’Diaye, email: [email protected]

Keywords: ovarian cancer; Store-operated calcium channels; mTORC1; MCL-1; ABT-737

Received: October 27, 2017 Accepted: August 04, 2018 Published: September 21, 2018

ABSTRACT

The anti-apoptotic proteins Bcl-x_L and Mcl-1 have been identified to play a pivotal role in apoptosis resistance in ovarian cancer and constitute key targets for innovative therapeutic strategies. Although BH3-mimetics (i.e. ABT-737) potently inhibit Bcl-x_L activity, targeting Mcl-1 remains a hurdle to the success of these strategies. Calcium signaling is profoundly remodeled during carcinogenesis and was reported to activate the signaling pathway controlling Mcl-1 expression. In this context, we investigated the effect of carboxyamidotriazole (CAI), a calcium channel inhibitor used in clinical trials, on Mcl-1 expression. CAI had an anti-proliferative effect on ovarian carcinoma cell lines and strongly down-regulated Mcl-1 expression. It inhibited store-operated calcium entry (SOCE) and Mcl-1 translation through mTORC1 deactivation. Moreover, it sensitized ovarian carcinoma cells to anti-Bcl-x_L strategies as their combination elicited massive apoptosis. Its effect on mTORC1 and Mcl-1 was mimicked by the potent SOCE inhibitor, YM58483, which also triggered apoptosis when combined with ABT-737. As a whole, this study suggests that CAI sensitizes to anti-Bcl-x_L strategies via its action on Mcl-1 translation and that modulation of SOCE could extend the therapeutic arsenal for treatment of ovarian carcinoma.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 26084

Publication Alerts

Research Papers:

Inhibition of store-operated channels by carboxyamidotriazole sensitizes ovarian carcinoma cells to anti-BclxL strategies through Mcl-1 down-regulation

Abstract

Inhibition of store-operated channels by carboxyamidotriazole sensitizes ovarian carcinoma cells to anti-Bclx_L strategies through Mcl-1 down-regulation