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 non-exposed cells, paralleled by mitochondrial Ca2+ uptake. Efficient Ca2+ efflux from 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 both in direct and indirect photodynamical cancer cell killing.

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

Nardin, Chiara
Investigation
;
Peres, Chiara
Membro del Collaboration Group
;
Ziraldo, Gaia
Membro del Collaboration Group
;
Mammano, Fabio
Supervision
2019

Abstract

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 non-exposed cells, paralleled by mitochondrial Ca2+ uptake. Efficient Ca2+ efflux from 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 both in direct and indirect photodynamical cancer cell killing.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3321801
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