Connexin Hemichannel Activation by S-Nitrosoglutathione Synergizes Strongly with Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing
Journal
Cancers
ISSN
2072-6694
Date Issued
2021
Author(s)
Chiara Nardin
Chiara Peres
Sabrina Putti
Tiziana Orsini
Claudia Colussi
Flavia Mazzarda
Marcello Raspa
Ferdinando Scavizzi
Anna Maria Salvatore
Francesco Chiani
Abraham Tettey-Matey
Yuanyuan Kuang
Guang Yang
Mauricio A. Retamal
Fabio Mammano
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>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.</jats:p>
Cite this document
Nardin, C., Peres, C., Putti, S., Orsini, T., Colussi, C., Mazzarda, F., Raspa, M., Scavizzi, F., Salvatore, A. M., Chiani, F., Tettey-Matey, A., Kuang, Y., Yang, G., Retamal, M. A., & Mammano, F. (2021). Connexin hemichannel activation by s-nitrosoglutathione synergizes strongly with photodynamic therapy potentiating anti-tumor bystander killing. Cancers, 13(20), 5062. https://doi.org/10.3390/cancers13205062
Subjects
photosensitization
;
nitric oxide
;
purinergic signaling
;
calcium signaling
;
adenosine triphosphate
;
gap junction protein
;
nitric oxide donor
;
photosensitizing agent
;
s nitrosoglutathione
;
animal cell
;
animal experiment
;
animal model
;
animal tissue
;
apoptosis
;
article
;
b16-f10 cell line
;
bystander effect (cell)
;
c57bl 6 mouse
;
calcium cell level
;
calcium signaling
;
cell death
;
controlled study
;
endoplasmic reticulum
;
in vivo study
;
male
;
mitochondrion
;
mouse
;
nonhuman
;
photoactivation
;
photodynamic therapy
;
protein expression
;
tumor microenvironment