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Comparative Study
. 2018 Jul;38(7):3843-3852.
doi: 10.21873/anticanres.12668.

Hydrogen Sulfide Is Increased in Oral Squamous Cell Carcinoma Compared to Adjacent Benign Oral Mucosae

Andrew T Meram  1 , Jie Chen  2 , Stavan Patel  1 , Dongsoo D Kim  1 , Brett Shirley  1 , Paul Covello  1 , Domenico Coppola  3 , Eric X Wei  2 , Ghali Ghali  1 , Christopher G Kevil  2 , Rodney E Shackelford  4
Affiliations
Comparative Study

Hydrogen Sulfide Is Increased in Oral Squamous Cell Carcinoma Compared to Adjacent Benign Oral Mucosae

Andrew T Meram et al. Anticancer Res. 2018 Jul.

Abstract

Background/aim: Hydrogen sulfide (H2S) and the enzymes that synthesize it, cystathionine-b-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate, are increased in different human malignancies. Due to its short half-life, H2S concentrations have not been directly measured in a human malignancy. Here we directly measured in vivo H2S levels within oral squamous cell carcinoma (OSCC).

Patients and methods: Punch biopsies of OSCC and benign mucosae from 15 patients were analyzed by HPLC, western blotting, and tissue microarray analyses.

Results: H2S concentrations were significantly higher in OSCC compared to adjacent benign oral mucosae. Western blot and tissue microarray studies revealed significantly increased cystathionine-b-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate, phopho-Stat3, mitoNEET, hTERT, and MAPK protein levels in OSCC.

Conclusion: H2S concentrations and the enzymes that synthesize it are significantly increased in OSCC. Here, for the first time H2S concentrations within a living human malignancy were measured and compared to adjacent counterpart benign tissue.

Keywords: 3-mercaptopyruvate; H2S; Hydrogen sulfide; cystathionine γ-lyase; cystathionine-β-synthase; mitoNEET.

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Conflict of interest statement

Conflicts of Interest

The Authors have no conflicts of interest regarding this work.

Figures

Figure 1.
Figure 1.
Representative immunostaining of benign oral squamous mucosae with CSE and 3-MST (A) and (B), respectively. Grade I (C and D), grade II (E and F), and grade III (G and H) OSCC were also stained for CSE and 3-MST, respectively. High-power views (×400).
Figure 2.
Figure 2.
Western blot analyses of benign oral mucosae and OSCC for the CBS (A), CSE (B), 3-MST (C), Nampt (D), mitoNEET (E), phospho-Stat3 (F), hTERT (G), MAPK (H), SQOR (I) and ATM (J) proteins. ***p<0.001. SQOR and ATM (2I and 2J) did not have statistically significant differences between benign oral epithelium and OSCC.
Figure 2.
Figure 2.
Western blot analyses of benign oral mucosae and OSCC for the CBS (A), CSE (B), 3-MST (C), Nampt (D), mitoNEET (E), phospho-Stat3 (F), hTERT (G), MAPK (H), SQOR (I) and ATM (J) proteins. ***p<0.001. SQOR and ATM (2I and 2J) did not have statistically significant differences between benign oral epithelium and OSCC.
Figure 3.
Figure 3.
Comparison of the cellular free sulfide (H2S) pools of benign oral mucosae and OSCC in fifteen patients. Free sulfide (H2S) is pmol/mg protein. *p<0.05.
See this image and copyright information in PMC

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