Hydrogen sulfide accelerates cell cycle progression in oral squamous cell carcinoma cell lines

Oral Dis. 2015 Mar;21(2):156-62. doi: 10.1111/odi.12223. Epub 2014 Mar 3.

Abstract

Objective: To investigate the cell cycle regulator role of the third gaseous transmitter hydrogen sulfide (H2 S) in three oral SCC cell lines by using NaHS, a donor of H2 S.

Methods: The synchronized oral squamous cell carcinoma cell lines (Cal27, GNM, and WSU-HN6) were treated with different concentrations of NaHS and then subjected to cell proliferation, cell cycle, and Western blot analyses.

Results: The CCK-8 assay results showed that the exogenously administered H2 S donor, NaHS, induced CAL-27, and GNM cell proliferation in a concentration-dependent manner, and the cell cycle analysis indicated that NaHS accelerated cell cycle progression of the synchronized CAL-27, GNM, and WSU-HN6 cells. Western blot analysis revealed that the cell cycle regulatory genes RPA70 and RB1 were significantly down-regulated and that proliferating cell nuclear antigen (PCNA) and CDK4 were markedly up-regulated by NaHS at specific time points in the cell cycle. In addition, our results indicated that the phosphorylation of Akt and Erk1/2 was involved in exogenous H2 S-induced oral SCC cell proliferation.

Conclusions: H2 S is a potential pro-proliferative factor of human oral SCC cells that accelerates the progression of the SCC cell cycle; thus, H2 S plays a deleterious role in oral SCC cancer development.

Keywords: cell cycle; hydrogen sulfide; proliferation; squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Cycle / drug effects*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase 4 / drug effects
  • Cyclin-Dependent Kinase 4 / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Hydrogen Sulfide / pharmacology*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Phosphorylation
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Replication Protein A / drug effects
  • Replication Protein A / genetics
  • Signal Transduction / drug effects
  • Squamous Cell Carcinoma of Head and Neck
  • Sulfides / pharmacology
  • Up-Regulation

Substances

  • Proliferating Cell Nuclear Antigen
  • RPA1 protein, human
  • Replication Protein A
  • Sulfides
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • sodium bisulfide
  • Hydrogen Sulfide