T-type calcium channel blockers inhibit autophagy and promote apoptosis of malignant melanoma cells.

Abstract:

:We have recently reported that human melanoma cells express a variety of voltage-gated calcium (Ca(2+) ) channel types, including low-voltage-activated T-type channels that play a significant role in melanoma cell cycle progression. Here, we challenged melanoma metastatic cells with T-type channel blockers of clinical use and found a dual effect on cell viability: (i) a reduction in the proliferation rate, through a halt in the progression to the G1 -S phase; and (ii) a promotion of cell death that was partially dependent on the activation of caspases. An in-depth analysis of the death process showed that the apoptotic pathway is preceded by endoplasmic reticulum stress and the subsequent inhibition of the basal macroautophagy which is active in these cells. The effects of pharmacological blockers on Ca(2+) homeostasis, autophagy, and cell death were mimicked by T-type channel gene silencing. These results provide the basis for a new pharmacological and/or gene silencing approach toward tackling melanoma metastasis.

authors

Das A,Pushparaj C,Herreros J,Nager M,Vilella R,Portero M,Pamplona R,Matias-Guiu X,Martí RM,Cantí C

doi

10.1111/pcmr.12155

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

874-85

issue

6

eissn

1755-1471

issn

1755-148X

journal_volume

26

pub_type

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