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T‐type calcium channel blockers inhibit autophagy and promote apoptosis of malignant melanoma cells
Author(s) -
Das Arindam,
Pushparaj Charumathi,
Herreros Judit,
Nager Mireia,
Vilella Ramon,
Portero Manuel,
Pamplona Reinald,
MatiasGuiu Xavier,
Martí Rosa M.,
Cantí Carles
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12155
Subject(s) - autophagy , melanoma , calcium channel , programmed cell death , apoptosis , cancer research , microbiology and biotechnology , gene silencing , voltage dependent calcium channel , biology , calcium , medicine , gene , biochemistry
Summary 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 G 1 ‐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.