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Photosensitizer Activation Drives Apoptosis by Interorganellar Ca2+ Transfer and Superoxide Production in Bystander Cancer Cells

1
Department of Physics and Astronomy “G. Galilei”, University of Padova, 35131 Padova, Italy
2
CNR Institute of Biochemistry and Cell Biology, 00015 Monterotondo, Rome, Italy
3
Department of Science, Roma Tre University, 00146 Rome, Italy
4
Institute of Otolaryngology, Catholic University of Rome, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
Cells 2019, 8(10), 1175; https://doi.org/10.3390/cells8101175
Received: 9 August 2019 / Revised: 14 September 2019 / Accepted: 27 September 2019 / Published: 29 September 2019
(This article belongs to the Special Issue Organellar Calcium Signaling in Physiology and Pathophysiology)
In cells, photosensitizer (PS) activation by visible light irradiation triggers reactive oxygen species (ROS) formation, followed by a cascade of cellular responses involving calcium (Ca2+) and other second messengers, resulting in cell demise. Cytotoxic effects spread to nearby cells not exposed to light by poorly characterized so-called “bystander effects”. To elucidate the mechanisms involved in bystander cell death, we used both genetically encoded biosensors and fluorescent dyes. In particular, we monitored the kinetics of interorganellar Ca2+ transfer and the production of mitochondrial superoxide anion (O2) and hydrogen peroxide (H2O2) in irradiated and bystander B16-F10 mouse melanoma cancer cells. We determined that focal PS photoactivation in a single cell triggers Ca2+ release from the endoplasmic reticulum (ER) also in the surrounding nonexposed cells, paralleled by mitochondrial Ca2+ uptake. Efficient Ca2+ efflux from the ER was required to promote mitochondrial O2 production in these bystander cells. Our results support a key role for ER–mitochondria communication in the induction of ROS-mediated apoptosis in both direct and indirect photodynamical cancer cell killing. View Full-Text
Keywords: bystander effect; organellar Ca2+; ROS; mitochondria; endoplasmic reticulum; biosensors; photodynamic therapy bystander effect; organellar Ca2+; ROS; mitochondria; endoplasmic reticulum; biosensors; photodynamic therapy
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Nardin, C.; Peres, C.; Mazzarda, F.; Ziraldo, G.; Salvatore, A.M.; Mammano, F. Photosensitizer Activation Drives Apoptosis by Interorganellar Ca2+ Transfer and Superoxide Production in Bystander Cancer Cells. Cells 2019, 8, 1175.

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