Connexin Hemichannel Activation by S-Nitrosoglutathione Synergizes Strongly with Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing

item.page.isbn

item.page.issn

item.page.issne

item.page.doiurl

item.page.other

item.page.references

Abstract

In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs). Intercellular calcium (Ca2+) waves propagated from irradiated to bystander cells promoting intracellular Ca2+ transfer from the endoplasmic reticulum (ER) to mitochondria and rapid activation of apoptotic pathways. Combination treatment with S-nitrosoglutathione (GSNO), an endogenous nitric oxide (NO) donor that biases HCs towards the open state, greatly potentiated anti-tumor bystander killing via enhanced Ca2+ signaling, leading to a significant reduction of post-irradiation tumor mass. Our results demonstrate that HCs can be exploited to dramatically increase cytotoxic bystander effects and reveal a previously unappreciated role for HCs in tumor eradication promoted by PDT.

Description

item.page.coverage.spatial

item.page.sponsorship

Citation

Nardin C, Peres C, Putti S, Orsini T, Colussi C, Mazzarda F, Raspa M, Scavizzi F, Salvatore AM, Chiani F, Tettey-Matey A, Kuang Y, Yang G, Retamal MA, Mammano F. Connexin Hemichannel Activation by S-Nitrosoglutathione Synergizes Strongly with Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing. Cancers (Basel). 2021 Oct 10;13(20):5062.

Keywords

Calcium signaling, Nitric oxide, Photosensitization, Purinergic signaling

item.page.dc.rights

item.page.dc.rights.url