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

Meram, Andrew T.; Chen, Jie; Patel, Stavan; Kim, Dongsoo D; Shirley, Brett; Covello, Paul; Coppola, Domenico; Wei, Eric; Ghali, Ghali; Kevil, Christopher G.; Shackelford, Rodney E.

doi:10.21873/anticanres.12668

Cited by 24 publications

(42 citation statements)

References 40 publications

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“…3-MST expression was also clearly demonstrated in many different primary tumor tissues, including human brain gliomas [33], human melanoma specimens [34], human colon cancer resections [26], human lung carcinoma resections [27], human urothelial cell carcinoma of the bladder resections [30,31], human oral squamous cell carcinoma resections [35], and oral adenoid cystic carcinoma resections [36]. In many (but not all) of these studies, the expression of 3-MST tended to increase with higher grades of the malignancy.…”

Section: Discussionmentioning

confidence: 95%

Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics in Murine Colon Cancer Cells

et al. 2020

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3-mercaptopyruvate sulfurtransferase (3-MST) has emerged as one of the significant sources of biologically active sulfur species in various mammalian cells. The current study was designed to investigate the functional role of 3-MST's catalytic activity in the murine colon cancer cell line CT26. The novel pharmacological 3-MST inhibitor HMPSNE was used to assess cancer cell proliferation, migration and bioenergetics in vitro. Methods included measurements of cell viability (MTT and LDH assays), cell proliferation and in vitro wound healing (IncuCyte) and cellular bioenergetics (Seahorse extracellular flux analysis). 3-MST expression was detected by Western blotting; H 2 S production was measured by the fluorescent dye AzMC. The results show that CT26 cells express 3-MST protein and mRNA, as well as several enzymes involved in H 2 S degradation (TST, ETHE1). Pharmacological inhibition of 3-MST concentration-dependently suppressed H 2 S production and, at 100 and 300 µM, attenuated CT26 proliferation and migration. HMPSNE exerted a bell-shaped effect on several cellular bioenergetic parameters related to oxidative phosphorylation, while other bioenergetic parameters were either unaffected or inhibited at the highest concentration of the inhibitor tested (300 µM). In contrast to 3-MST, the expression of CBS (another H 2 S producing enzyme which has been previously implicated in the regulation of various biological parameters in other tumor cells) was not detectable in CT26 cells and pharmacological inhibition of CBS exerted no significant effects on CT26 proliferation or bioenergetics. In summary, 3-MST catalytic activity significantly contributes to the regulation of cellular proliferation, migration and bioenergetics in CT26 murine colon cancer cells. The current studies identify 3-MST as the principal source of biologically active H 2 S in this cell line.

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Section: Discussionmentioning

confidence: 95%

Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics in Murine Colon Cancer Cells

et al. 2020

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“…We also recovered proteins of the PI3K/AKT/mTOR and COX2/AKT/ERK1/2 pathways in H. dujardini and H. panicea that are potentially involved in the singlet oxygen damage resistance processes: NFkb1, BCL2, AKT, NOS1, CBS, BIRC5/Survivin, CTH, NAMPT, TST/ MPST, CDGSH/mitoNEET, MTOR [12][13][14][15]. All these proteins have good sequence similarity (60% to 85%) with the exception of apoptosis regulator BCL2.…”

Section: Iron Processing In Spongesmentioning

confidence: 99%

“…The intracellular iron-containing photosensitizer protoporphyrin IX (PpIX) is the immediate precursor of heme, which serves as a cofactor to a functional core of proteins involved in storage and delivery of molecular oxygen. Excess of PpIX damages mitochondria [10,11], and its suppression is one of the major defense mechanisms against damages caused by singlet oxygen in mammalian tumors [12,13]. The outer mitochondrial membrane iron-sulfur protein Mito-NEET controls intramitochondrial iron concentrations and allows tumor cells to tolerate reactive oxygen species and to avoid ferroptosis via activation of the PI3K/Akt/mTOR and COX2/ AKT/ERK1/2 pathways [12,14,15].…”

Section: Introductionmentioning

confidence: 99%

“…Excess of PpIX damages mitochondria [10,11], and its suppression is one of the major defense mechanisms against damages caused by singlet oxygen in mammalian tumors [12,13]. The outer mitochondrial membrane iron-sulfur protein Mito-NEET controls intramitochondrial iron concentrations and allows tumor cells to tolerate reactive oxygen species and to avoid ferroptosis via activation of the PI3K/Akt/mTOR and COX2/ AKT/ERK1/2 pathways [12,14,15]. At low oxygen availability, the hypoxia-inducible factors (HIFs) regulate the expression of genes that mediate cell's adaptive responses connected to mitochondrial function, energy metabolism, oxygen binding and delivery [2,[16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Iron metabolic pathways in the processes of sponge plasticity

et al. 2020

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The ability to regulate oxygen consumption evolved in ancestral animals and is intrinsically linked to iron metabolism. The iron pathways have been intensively studied in mammals, whereas data on distant invertebrates are limited. Sea sponges represent the oldest animal phylum and have unique structural plasticity and capacity to reaggregate after complete dissociation. We studied iron metabolic factors and their expression during reaggregation in the White Sea cold-water sponges Halichondria panicea and Halisarca dujardini. De novo transcriptomes were assembled using RNA-Seq data, and evolutionary trends were analyzed with bioinformatic tools. Differential expression during reaggregation was studied for H. dujardini. Enzymes of the heme biosynthesis pathway and transport globins, neuroglobin (NGB) and androglobin (ADGB), were identified in sponges. The globins mutate at higher evolutionary rates than the heme synthesis enzymes. Highly conserved iron-regulatory protein 1 (IRP1) presumably interacts with the iron-responsive elements (IREs) found in mRNAs of ferritin (FTH1) and a putative transferrin receptor NAALAD2. The reaggregation process is accompanied by increased expression of IRP1, the antiapoptotic factor BCL2, the inflammation factor NFκB (p65), FTH1 and NGB, as well as by an increase in mitochondrial density. Our data indicate a complex mechanism of iron regulation in sponge structural plasticity and help to better understand general mechanisms of morphogenetic processes in multicellular species.

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“…Cystathione β-synthase (CBS) catalyzes the conversion of homocysteine and cysteine to hydrogen sulfide (H 2 S) and cystathione, via the trans-sulfuration pathway (14). CBS is increased in several human malignancies, including colon, ovarian, bladder, breast, renal cell, and oral squamous cell carcinomas (15)(16)(17)(18)(19)(20). Higher CBS level correlates with increased clinical aggressiveness in several different malignancies (15,16,18,20).…”

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confidence: 99%

Cystathione β-Synthase Is Increased in Thyroid Malignancies

et al. 2018

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Background: Cystathione β-synthase (CBS) catalyzes the conversion of homocysteine and cysteine to hydrogen sulfide (H 2 S) and cystathione, via the transsulfuration pathway. CBS protein expression levels are increased in several different human malignancies, with increased protein expression correlating with parameters such as tumor stage, anaplasia, metastases, and chemotherapy resistance. Materials and Methods: This study employed tissue microarrays to examine CBS expression in benign thyroid tissue, thyroid oncocytomas, thyroid follicular adenomas, and in follicular, papillary, anaplastic, and medullary thyroid carcinomas. Results: CBS expression was increased in all thyroid carcinomas types compared to benign thyroid tissue, but not in thyroid follicular adenomas or oncocytomas. A similar pattern was observed for nicotinamide phosphoribosyltransferase (NAMPT) tissue microarray analysis comparing thyroid adenomas and follicular carcinomas. Conclusion: For the first time, we showed that an H 2 S-syntheszing enzyme plays a role in thyroid malignancies. Additionally, our data suggest that CBS and NAMPT immunohistochemistry may be useful in differentiating follicular adenomas from follicular carcinomas.

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

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

Cited by 24 publications

References 40 publications

Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics in Murine Colon Cancer Cells

Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics in Murine Colon Cancer Cells

Iron metabolic pathways in the processes of sponge plasticity

Cystathione β-Synthase Is Increased in Thyroid Malignancies

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