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Role of endogenous and exogenous nitric oxide, carbon monoxide and hydrogen sulfide in HCT116 colon cancer cell proliferation.
Biochem Pharmacol. 2018 03; 149:186-204.BP

Abstract

The role of the three gasotransmitter systems - nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) - in cancer cells has not yet been studied simultaneously in the same experimental system. We measured the expression of NO and CO and H2S generating enzymes in primary colon cancer tissues and HCT116 colon cancer cells, and evaluated the effect of their pharmacological inhibition or pharmacological donation on cell proliferation. Increased expression of iNOS, nNOS, HO-1, CBS and 3-MST was detected in colon cancer. Inhibitors of NOS, HO-1/2, CBS/CSE and 3-MST, at lower concentrations, slightly stimulated HCT116 cell proliferation, but inhibited proliferation at higher concentrations. Donors of NO, CO or H2S inhibited HCT116 proliferation in a concentration-dependent manner. Inhibition of the cGMP/VASP pathway, Akt and p44/42 MAPK (Erk1/2) inhibited HCT116 cell proliferation. Endogenous NO and H2S biosynthesis were found to play a role in the maintenance of the activity of the cGMP/VASP pathway in HCT116 cells. We conclude that each of the three gasotransmitters play similar, bell-shaped roles in the control of HCT116 cell proliferation: endogenously produced NO, CO and H2S, at an optimal concentration, support HCT116 proliferation; inhibition of their production (which decreases gasotransmitter levels below optimal concentrations) as well as exogenous delivery of these gasotransmitters (which increases gasotransmitter levels above optimal concentrations) suppresses colon cancer cell proliferation. The current data give a mechanistic explanation for the paradoxical finding that both inhibitors and donors of NO, CO and H2S exert anticancer actions in cancer cells.

Authors+Show Affiliations

Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA; Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: szabocsaba@aol.com.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29074106

Citation

Oláh, Gabor, et al. "Role of Endogenous and Exogenous Nitric Oxide, Carbon Monoxide and Hydrogen Sulfide in HCT116 Colon Cancer Cell Proliferation." Biochemical Pharmacology, vol. 149, 2018, pp. 186-204.
Oláh G, Módis K, Törö G, et al. Role of endogenous and exogenous nitric oxide, carbon monoxide and hydrogen sulfide in HCT116 colon cancer cell proliferation. Biochem Pharmacol. 2018;149:186-204.
Oláh, G., Módis, K., Törö, G., Hellmich, M. R., Szczesny, B., & Szabo, C. (2018). Role of endogenous and exogenous nitric oxide, carbon monoxide and hydrogen sulfide in HCT116 colon cancer cell proliferation. Biochemical Pharmacology, 149, 186-204. https://doi.org/10.1016/j.bcp.2017.10.011
Oláh G, et al. Role of Endogenous and Exogenous Nitric Oxide, Carbon Monoxide and Hydrogen Sulfide in HCT116 Colon Cancer Cell Proliferation. Biochem Pharmacol. 2018;149:186-204. PubMed PMID: 29074106.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of endogenous and exogenous nitric oxide, carbon monoxide and hydrogen sulfide in HCT116 colon cancer cell proliferation. AU - Oláh,Gabor, AU - Módis,Katalin, AU - Törö,Gabor, AU - Hellmich,Mark R, AU - Szczesny,Bartosz, AU - Szabo,Csaba, Y1 - 2017/10/23/ PY - 2017/09/19/received PY - 2017/10/20/accepted PY - 2017/10/28/pubmed PY - 2018/12/12/medline PY - 2017/10/28/entrez KW - Anticancer KW - Apoptosis KW - Bioenergetics KW - Cancer KW - Cell proliferation KW - Gasotransmitters KW - PI3K KW - Signaling SP - 186 EP - 204 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 149 N2 - The role of the three gasotransmitter systems - nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) - in cancer cells has not yet been studied simultaneously in the same experimental system. We measured the expression of NO and CO and H2S generating enzymes in primary colon cancer tissues and HCT116 colon cancer cells, and evaluated the effect of their pharmacological inhibition or pharmacological donation on cell proliferation. Increased expression of iNOS, nNOS, HO-1, CBS and 3-MST was detected in colon cancer. Inhibitors of NOS, HO-1/2, CBS/CSE and 3-MST, at lower concentrations, slightly stimulated HCT116 cell proliferation, but inhibited proliferation at higher concentrations. Donors of NO, CO or H2S inhibited HCT116 proliferation in a concentration-dependent manner. Inhibition of the cGMP/VASP pathway, Akt and p44/42 MAPK (Erk1/2) inhibited HCT116 cell proliferation. Endogenous NO and H2S biosynthesis were found to play a role in the maintenance of the activity of the cGMP/VASP pathway in HCT116 cells. We conclude that each of the three gasotransmitters play similar, bell-shaped roles in the control of HCT116 cell proliferation: endogenously produced NO, CO and H2S, at an optimal concentration, support HCT116 proliferation; inhibition of their production (which decreases gasotransmitter levels below optimal concentrations) as well as exogenous delivery of these gasotransmitters (which increases gasotransmitter levels above optimal concentrations) suppresses colon cancer cell proliferation. The current data give a mechanistic explanation for the paradoxical finding that both inhibitors and donors of NO, CO and H2S exert anticancer actions in cancer cells. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/29074106/Role_of_endogenous_and_exogenous_nitric_oxide_carbon_monoxide_and_hydrogen_sulfide_in_HCT116_colon_cancer_cell_proliferation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(17)30642-1 DB - PRIME DP - Unbound Medicine ER -