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Connexin Hemichannel Activation by S-Nitrosoglutathione Synergizes Strongly with Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing.
Nardin, Chiara; Peres, Chiara; Putti, Sabrina; Orsini, Tiziana; Colussi, Claudia; Mazzarda, Flavia; Raspa, Marcello; Scavizzi, Ferdinando; Salvatore, Anna Maria; Chiani, Francesco; Tettey-Matey, Abraham; Kuang, Yuanyuan; Yang, Guang; Retamal, Mauricio A; Mammano, Fabio.
Afiliación
  • Nardin C; Institute of Biochemistry and Cell Biology (IBBC)-CNR, 00015 Rome, Italy.
  • Peres C; Institute of Biochemistry and Cell Biology (IBBC)-CNR, 00015 Rome, Italy.
  • Putti S; Institute of Biochemistry and Cell Biology (IBBC)-CNR, 00015 Rome, Italy.
  • Orsini T; Institute of Biochemistry and Cell Biology (IBBC)-CNR, 00015 Rome, Italy.
  • Colussi C; Institute for Systems Analysis and Computer Science "A. Ruberti" (IASI)-CNR, 00168 Rome, Italy.
  • Mazzarda F; Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of the Sacred Heart, 00168 Rome, Italy.
  • Raspa M; Institute of Biochemistry and Cell Biology (IBBC)-CNR, 00015 Rome, Italy.
  • Scavizzi F; Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
  • Salvatore AM; Institute of Biochemistry and Cell Biology (IBBC)-CNR, 00015 Rome, Italy.
  • Chiani F; Institute of Biochemistry and Cell Biology (IBBC)-CNR, 00015 Rome, Italy.
  • Tettey-Matey A; Institute of Biochemistry and Cell Biology (IBBC)-CNR, 00015 Rome, Italy.
  • Kuang Y; Institute of Biochemistry and Cell Biology (IBBC)-CNR, 00015 Rome, Italy.
  • Yang G; Institute of Biochemistry and Cell Biology (IBBC)-CNR, 00015 Rome, Italy.
  • Retamal MA; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.
  • Mammano F; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.
Cancers (Basel) ; 13(20)2021 Oct 10.
Article en En | MEDLINE | ID: mdl-34680212
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza