{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T19:34:21Z","timestamp":1785094461354,"version":"3.55.0"},"reference-count":113,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education, University and Research (MIUR)","award":["Dipartimenti di Eccellenza Program (2018\u20132022) - Dept. of Biology and Biotechnology \"L. Spallanzani\", University of Pavia"],"award-info":[{"award-number":["Dipartimenti di Eccellenza Program (2018\u20132022) - Dept. of Biology and Biotechnology \"L. Spallanzani\", University of Pavia"]}]},{"DOI":"10.13039\/501100004769","name":"University of Pavia","doi-asserted-by":"publisher","award":["Fondo Ricerca Giovani"],"award-info":[{"award-number":["Fondo Ricerca Giovani"]}],"id":[{"id":"10.13039\/501100004769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IRCCS Foundations Policlinico San Matteo","award":["RC\/08059815B"],"award-info":[{"award-number":["RC\/08059815B"]}]},{"name":"IRCCS Foundations Policlinico San Matteo","award":["RF-2011-02352315"],"award-info":[{"award-number":["RF-2011-02352315"]}]},{"name":"Italian Ministry of Health Grants","award":["RF-2010-2316319"],"award-info":[{"award-number":["RF-2010-2316319"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Exogenous administration of hydrogen sulfide (H2S) is emerging as an alternative anticancer treatment. H2S-releasing compounds have been shown to exert a strong anticancer effect by suppressing proliferation and\/or inducing apoptosis in several cancer cell types, including colorectal carcinoma (CRC). The mechanism whereby exogenous H2S affects CRC cell proliferation is yet to be clearly elucidated, but it could involve an increase in intracellular Ca2+ concentration ([Ca2+]i). Herein, we sought to assess for the first time whether (and how) sodium hydrosulfide (NaHS), one of the most widely employed H2S donors, induced intracellular Ca2+ signals in primary cultures of human metastatic CRC (mCRC) cells. We provided the evidence that NaHS induced extracellular Ca2+ entry in mCRC cells by activating the Ca2+-permeable channel Transient Receptor Potential Vanilloid 1 (TRPV1) followed by the Na+-dependent recruitment of the reverse-mode of the Na+\/Ca2+ (NCX) exchanger. In agreement with these observations, TRPV1 protein was expressed and capsaicin, a selective TRPV1 agonist, induced Ca2+ influx by engaging both TRPV1 and NCX in mCRC cells. Finally, NaHS reduced mCRC cell proliferation, but did not promote apoptosis or aberrant mitochondrial depolarization. These data support the notion that exogenous administration of H2S may prevent mCRC cell proliferation through an increase in [Ca2+]i, which is triggered by TRPV1.<\/jats:p>","DOI":"10.3390\/cancers12113338","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T19:08:28Z","timestamp":1605121708000},"page":"3338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Hydrogen Sulfide-Evoked Intracellular Ca2+ Signals in Primary Cultures of Metastatic Colorectal Cancer Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6867-0359","authenticated-orcid":false,"given":"Pawan","family":"Faris","sequence":"first","affiliation":[{"name":"Laboratory of General Physiology, Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"},{"name":"Department of Biology, Cihan University-Erbil, 44001 Erbil, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Ferulli","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Vismara","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Tanzi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Negri","sequence":"additional","affiliation":[{"name":"Laboratory of General Physiology, Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Rumolo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kostantinos","family":"Lefkimmiatis","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy"},{"name":"Veneto Institute of Molecular Medicine, Foundation for Advanced Biomedical Research, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Maestri","sequence":"additional","affiliation":[{"name":"Medical Surgery, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9552-838X","authenticated-orcid":false,"given":"Mudhir","family":"Shekha","sequence":"additional","affiliation":[{"name":"Faculty of Science, Department of Medical Analysis, Tishk International University-Erbil, 44001 Erbil, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9419-7160","authenticated-orcid":false,"given":"Paolo","family":"Pedrazzoli","sequence":"additional","affiliation":[{"name":"Medical Oncology, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-4564","authenticated-orcid":false,"given":"Gianni Francesco","family":"Guidetti","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Montagna","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, Italy"},{"name":"Diagnostic and Pediatric, Department of Sciences Clinic-Surgical, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-0098","authenticated-orcid":false,"given":"Francesco","family":"Moccia","sequence":"additional","affiliation":[{"name":"Laboratory of General Physiology, Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/jso.24578","article-title":"Colorectal cancer-global burden, trends, and geographical variations","volume":"115","author":"Douaiher","year":"2017","journal-title":"J. Surg. Oncol."},{"key":"ref_2","first-page":"S42","article-title":"Adjuvant treatment of colorectal cancer","volume":"2","author":"Carrato","year":"2008","journal-title":"Gastrointest. Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nrm3391","article-title":"H2S signalling through protein sulfhydration and beyond","volume":"13","author":"Paul","year":"2012","journal-title":"Nat. Rev. Mol. 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