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Correction published on 23 July 2020, see Cancers 2020, 12(8), 2023.
Article

Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma

Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels 1200, Belgium
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(3), 430; https://doi.org/10.3390/cancers11030430
Received: 14 February 2019 / Revised: 19 March 2019 / Accepted: 22 March 2019 / Published: 26 March 2019
(This article belongs to the Special Issue Ion Channels in Cancer)
Cisplatin (CDDP) is one of the principal chemotherapeutic agents used for the first-line treatment of many malignancies, including non-small cell lung carcinoma (NSCLC). Despite its use for over 40 years, its mechanism of action is not yet fully understood. Store-operated calcium entry (SOCE), the main pathway allowing Ca2+ entry in non-excitable cells, is involved in tumorogenesis, cancer progression and chemoresistance. It has become an attractive target in cancer treatment. In this study, we showed that siRNA-mediated depletion of stromal interaction molecule 1 (STIM1) and transient receptor potential channel 1 (TRPC1), two players of the store-operated calcium entry, dramatically reduced CDDP cytotoxicity in NSCLC cells. This was associated with an inhibition of the DNA damage response (DDR) triggered by CDDP. Moreover, STIM1 depletion also reduced CDDP-dependent oxidative stress. In parallel, SOCE activation induced Ca2+ entry into the mitochondria, a major source of reactive oxygen species (ROS) within the cell. This effect was highly decreased in STIM1-depleted cells. We then conclude that mitochondrial Ca2+ peak associated to the SOCE contributes to CDDP-induced ROS production, DDR and subsequent apoptosis. To the best of our knowledge, this is the first time that it is shown that Ca2+ signalling constitutes an initial step in CDDP-induced apoptosis. View Full-Text
Keywords: store-operated calcium entry; cisplatin; apoptosis; reactive oxygen species; mitochondrial calcium; non-small cell lung carcinoma store-operated calcium entry; cisplatin; apoptosis; reactive oxygen species; mitochondrial calcium; non-small cell lung carcinoma
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MDPI and ACS Style

Gualdani, R.; de Clippele, M.; Ratbi, I.; Gailly, P.; Tajeddine, N. Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma. Cancers 2019, 11, 430. https://doi.org/10.3390/cancers11030430

AMA Style

Gualdani R, de Clippele M, Ratbi I, Gailly P, Tajeddine N. Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma. Cancers. 2019; 11(3):430. https://doi.org/10.3390/cancers11030430

Chicago/Turabian Style

Gualdani, Roberta, Marie de Clippele, Ikram Ratbi, Philippe Gailly, and Nicolas Tajeddine. 2019. "Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma" Cancers 11, no. 3: 430. https://doi.org/10.3390/cancers11030430

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