Hydrogen Sulfide-Evoked Intracellular Ca<sup>2+</sup> Signals in Primary Cultures of Metastatic Colorectal Cancer Cells
Exogenous administration of hydrogen sulfide (H<sub>2</sub>S) is emerging as an alternative anticancer treatment. H<sub>2</sub>S-releasing compounds have been shown to exert a strong anticancer effect by suppressing proliferation and/or inducing apoptosis in several cancer ce...
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Online Access: | https://www.mdpi.com/2072-6694/12/11/3338 |
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doaj-3cbfae85ce7243ed9a7d2f0531ca41762020-11-25T04:00:24ZengMDPI AGCancers2072-66942020-11-01123338333810.3390/cancers12113338Hydrogen Sulfide-Evoked Intracellular Ca<sup>2+</sup> Signals in Primary Cultures of Metastatic Colorectal Cancer CellsPawan Faris0Federica Ferulli1Mauro Vismara2Matteo Tanzi3Sharon Negri4Agnese Rumolo5Kostantinos Lefkimmiatis6Marcello Maestri7Mudhir Shekha8Paolo Pedrazzoli9Gianni Francesco Guidetti10Daniela Montagna11Francesco Moccia12Laboratory of General Physiology, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyLaboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, ItalyLaboratory of Biochemistry, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyLaboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, ItalyLaboratory of General Physiology, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyLaboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyMedical Surgery, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, ItalyFaculty of Science, Department of Medical Analysis, Tishk International University-Erbil, 44001 Erbil, IraqMedical Oncology, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, ItalyLaboratory of Biochemistry, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyLaboratory of Immunology Transplantation, Foundation IRCCS Policlinico San Matteo, 27100 Pavia, ItalyLaboratory of General Physiology, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyExogenous administration of hydrogen sulfide (H<sub>2</sub>S) is emerging as an alternative anticancer treatment. H<sub>2</sub>S-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 H<sub>2</sub>S affects CRC cell proliferation is yet to be clearly elucidated, but it could involve an increase in intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>). Herein, we sought to assess for the first time whether (and how) sodium hydrosulfide (NaHS), one of the most widely employed H<sub>2</sub>S donors, induced intracellular Ca<sup>2+</sup> signals in primary cultures of human metastatic CRC (mCRC) cells. We provided the evidence that NaHS induced extracellular Ca<sup>2+</sup> entry in mCRC cells by activating the Ca<sup>2+</sup>-permeable channel Transient Receptor Potential Vanilloid 1 (TRPV1) followed by the Na<sup>+</sup>-dependent recruitment of the reverse-mode of the Na<sup>+</sup>/Ca<sup>2+</sup> (NCX) exchanger. In agreement with these observations, TRPV1 protein was expressed and capsaicin, a selective TRPV1 agonist, induced Ca<sup>2+</sup> 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 H<sub>2</sub>S may prevent mCRC cell proliferation through an increase in [Ca<sup>2+</sup>]<sub>i</sub>, which is triggered by TRPV1.https://www.mdpi.com/2072-6694/12/11/3338H2STRPV1NCXcancermetastatic colorectal carcinomaproliferation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Hydrogen Sulfide-Evoked Intracellular Ca<sup>2+</sup> Signals in Primary Cultures of Metastatic Colorectal Cancer Cells Cancers H2S TRPV1 NCX cancer metastatic colorectal carcinoma proliferation |
author_facet |
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 |
author_sort |
Pawan Faris |
title |
Hydrogen Sulfide-Evoked Intracellular Ca<sup>2+</sup> Signals in Primary Cultures of Metastatic Colorectal Cancer Cells |
title_short |
Hydrogen Sulfide-Evoked Intracellular Ca<sup>2+</sup> Signals in Primary Cultures of Metastatic Colorectal Cancer Cells |
title_full |
Hydrogen Sulfide-Evoked Intracellular Ca<sup>2+</sup> Signals in Primary Cultures of Metastatic Colorectal Cancer Cells |
title_fullStr |
Hydrogen Sulfide-Evoked Intracellular Ca<sup>2+</sup> Signals in Primary Cultures of Metastatic Colorectal Cancer Cells |
title_full_unstemmed |
Hydrogen Sulfide-Evoked Intracellular Ca<sup>2+</sup> Signals in Primary Cultures of Metastatic Colorectal Cancer Cells |
title_sort |
hydrogen sulfide-evoked intracellular ca<sup>2+</sup> signals in primary cultures of metastatic colorectal cancer cells |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-11-01 |
description |
Exogenous administration of hydrogen sulfide (H<sub>2</sub>S) is emerging as an alternative anticancer treatment. H<sub>2</sub>S-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 H<sub>2</sub>S affects CRC cell proliferation is yet to be clearly elucidated, but it could involve an increase in intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>). Herein, we sought to assess for the first time whether (and how) sodium hydrosulfide (NaHS), one of the most widely employed H<sub>2</sub>S donors, induced intracellular Ca<sup>2+</sup> signals in primary cultures of human metastatic CRC (mCRC) cells. We provided the evidence that NaHS induced extracellular Ca<sup>2+</sup> entry in mCRC cells by activating the Ca<sup>2+</sup>-permeable channel Transient Receptor Potential Vanilloid 1 (TRPV1) followed by the Na<sup>+</sup>-dependent recruitment of the reverse-mode of the Na<sup>+</sup>/Ca<sup>2+</sup> (NCX) exchanger. In agreement with these observations, TRPV1 protein was expressed and capsaicin, a selective TRPV1 agonist, induced Ca<sup>2+</sup> 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 H<sub>2</sub>S may prevent mCRC cell proliferation through an increase in [Ca<sup>2+</sup>]<sub>i</sub>, which is triggered by TRPV1. |
topic |
H2S TRPV1 NCX cancer metastatic colorectal carcinoma proliferation |
url |
https://www.mdpi.com/2072-6694/12/11/3338 |
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