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

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dc.contributor.authorNardin, Chiara
dc.contributor.authorPeres, Chiara
dc.contributor.authorPutti, Sabrina
dc.contributor.authorOrsini, Tiziana
dc.contributor.authorColussi, Claudia
dc.contributor.authorMazzarda, Flavia
dc.contributor.authorRaspa, Marcello
dc.contributor.authorScavizzi, Ferdinando
dc.contributor.authorSalvatore, Anna María
dc.contributor.authorChiani, Francesco
dc.contributor.authorTettey-Matey, Abraham
dc.contributor.authorKuang, Yuanyuan
dc.contributor.authorYang, Guang
dc.contributor.authorRetamal, Mauricio
dc.contributor.authorMammano, Fabio
dc.date.accessioned2021-11-25T19:42:36Z
dc.date.available2021-11-25T19:42:36Z
dc.date.issued2021
dc.description.abstractIn 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.es
dc.identifier.citationNardin 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.es
dc.identifier.urihttps://doi.org/10.3390/cancers13205062es
dc.identifier.urihttp://hdl.handle.net/11447/5110
dc.language.isoenes
dc.subjectCalcium signalinges
dc.subjectNitric oxidees
dc.subjectPhotosensitizationes
dc.subjectPurinergic signalinges
dc.titleConnexin Hemichannel Activation by S-Nitrosoglutathione Synergizes Strongly with Photodynamic Therapy Potentiating Anti-Tumor Bystander Killinges
dc.typeArticlees

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