Hydrogen sulfide-evoked intracellular ca2+ signals in primary cultures of metastatic colorectal cancer cells

Pawan Faris, Federica Ferulli, Mauro Vismara, Matteo Tanzi, Sharon Negri, Agnese Rumolo, Kostantinos Lefkimmiatis, Marcello Maestri, Mudhir Shekha, Paolo Pedrazzoli, Gianni Francesco Guidetti, Daniela Montagna, Francesco Moccia

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number3338
Pages (from-to)1-27
Number of pages27
Issue number11
Publication statusPublished - Nov 2020


  • Cancer
  • H2S
  • Metastatic colorectal carcinoma
  • NCX
  • Proliferation
  • TRPV1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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