H2S Donor, S-Propargyl-Cysteine, Increases CSE in SGC-7901 and Cancer-Induced Mice: Evidence for a Novel Anti-Cancer Effect of Endogenous H2S?

Ma, Kaium; Liu, Yan; Zhu, Qing; Liu, Chunhua; Duan, Jun‐Li; Tan, Benny K.H.; Zhu, Yi Zhun

doi:10.1371/journal.pone.0020525

Cited by 97 publications

(79 citation statements)

References 31 publications

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“…Our research (31) and other studies (24)(25)(26)(27)(28)(29)(30) suggest that H 2 S is beneficial for cancer cells growth, proliferation, migration and invasion. On the contrary, some other researchers found that H 2 S exerted potential anticancer efficiency in SGC-7901 gastric cancer cells (40), oral cancer cell lines (41), colon cancer cells (42), and in several different human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11 and U2OS) (43). As the above is contradictory further research must be carried out to clarify these issues.…”

Section: Discussionmentioning

confidence: 92%

Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways

et al. 2015

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Abstract. Hydrogen sulfide (H 2 S) participates in multifarious physiological and pathophysiologic progresses of cancer both in vitro and in vivo.We have previously demonstrated that exogenous H 2 S promoted liver cancer cells proliferation/anti-apoptosis/angiogenesis/migration effects via amplifying the activation of NF-κB pathway. However, the effects of H 2 S on cancer cell proliferation and apoptosis are controversial and remain unclear in C6 glioma cells. The present study investigated the effects of exogenous H 2 S on cancer cells growth via activating p38 MAPK/ERK1/2-COX-2 pathways in C6 glioma cells. C6 glioma cells were treated with 400 µmol/l NaHS (a donor of H 2 S) for 24 h. The expression levels of phosphorylated (p)-p38 MAPK, total (t)-p38 MAPK, p-ERK1/2, t-ERK1/2, cyclooxygenase-2 (COX-2) and caspase-3 were measured by western blotting assay. Cell viability was detected by Cell Counting . Apoptotic cells were observed by Hoechst 33258 staining assay. Cell proliferation was directly detected under fully automatic inverted microscope. Exposure of C6 glioma cells to NaHS resulted in cell proliferation, as evidenced by an increase in cell viability. In addition, NaHS treatment reduced apoptosis, as indicated by the decreased apoptotic percentage and the cleaved caspase-3 expression. Importantly, exposure of the cells to NaHS increased the expression levels of p-p38 MAPK, p-ERK1/2 and COX-2. Notably, co-treatment of C6 glioma cells with 400 µmol/l NaHS and AOAA (an inhibitor of CBS) largely suppressed the above NaHS-induced effects. Combined treatment with NaHS and SB203580 (an inhibitor of p38 MAPK) or PD-98059 (an inhibitor of ERK1/2) resulted in the synergistic reduction of COX-2 expression and increase of caspase-3 expression, a decreased number of apoptotic cells, along with decreased cell viability. Combined treatment with NS-398 (an inhibitor of COX-2) and NaHS also resulted in the synergistic increase of caspase-3, a decreased in the number of apoptotic cells and the decrease in cell viability. The findings of the present study provide novel evidence that p38 MAPK/ERK1/2-COX-2 pathways are involved in NaHS-induced cancer cell proliferation and anti-apoptosis in C6 glioma cells.

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Section: Discussionmentioning

confidence: 92%

Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways

et al. 2015

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“…For these reasons, we have excluded the combined molecules mentioned earlier from our present analysis. In another study, Ma et al report on the anticancer effect of the garlic extract component S-propargylcysteine (72). Although this compound is often discussed as a H 2 S pathway modulator, its pharmacological profile is extremely complex, as it includes kinase activation, up-regulation of CSE, and many other actions (9,72).…”

Section: H 2 S Donation Versus H 2 S Biosynthesis Inhibition In Cancermentioning

confidence: 99%

“…In another study, Ma et al report on the anticancer effect of the garlic extract component S-propargylcysteine (72). Although this compound is often discussed as a H 2 S pathway modulator, its pharmacological profile is extremely complex, as it includes kinase activation, up-regulation of CSE, and many other actions (9,72). Thus, while the compound can induce apoptosis in vitro and may reduce tumors in vivo, we believe that its actions are too complex to be evaluated in the current review.…”

Section: H 2 S Donation Versus H 2 S Biosynthesis Inhibition In Cancermentioning

confidence: 99%

The Therapeutic Potential of Cystathionine β-Synthetase/Hydrogen Sulfide Inhibition in Cancer

Hellmich

Coletta

Chao

et al. 2015

Antioxidants & Redox Signaling

204

186

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Significance: Cancer represents a major socioeconomic problem; there is a significant need for novel therapeutic approaches targeting tumor-specific pathways. Recent Advances: In colorectal and ovarian cancers, an increase in the intratumor production of hydrogen sulfide (H 2 S) from cystathionine b-synthase (CBS) plays an important role in promoting the cellular bioenergetics, proliferation, and migration of cancer cells. It also stimulates peritumor angiogenesis inhibition or genetic silencing of CBS exerts antitumor effects both in vitro and in vivo, and potentiates the antitumor efficacy of anticancer therapeutics. Critical Issues: Recently published studies are reviewed, implicating CBS overexpression and H 2 S overproduction in tumor cells as a tumorgrowth promoting ''bioenergetic fuel'' and ''survival factor,'' followed by an overview of the experimental evidence demonstrating the anticancer effect of CBS inhibition. Next, the current state of the art of pharmacological CBS inhibitors is reviewed, with special reference to the complex pharmacological actions of aminooxyacetic acid. Finally, new experimental evidence is presented to reconcile a controversy in the literature regarding the effects of H 2 S donor on cancer cell proliferation and survival. Future Directions: From a basic science standpoint, future directions in the field include the delineation of the molecular mechanism of CBS upregulation of cancer cells and the delineation of the interactions of H 2 S with other intracellular pathways of cancer cell metabolism and proliferation. From the translational science standpoint, future directions include the translation of the recently emerging roles of H 2 S in cancer into human diagnostic and therapeutic approaches. Antioxid. Redox Signal. 22,

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“…It has been reported that the increased H 2 S production plays a crucial role in cell proliferation and the related angiogenesis in several types of cancer cell lines, such as colonic and ovarian cancers. 18,19) In addition, there are many papers showing that endogenous or exogenous H 2 S modulates cell proliferation and migration in gastric, oral, breast, pancreas, lung or prostate cancer and also leukemia, 12,[20][21][22] whereas, H 2 S promotes and suppresses cancer growth in distinct cells. Thus, the effects of H 2 S on cancers might vary with the tissues, conditions surrounding cancer, the amount of synthesized H 2 S, and so on.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, there are inconsistent papers concerning the effects of H 2 S on gastric cancer cell proliferation and related angiogenesis. 12,13) In the present study, we evaluated the role of endogenous H 2 S in gastric cancer proliferations in human gastric cancer AGS cells. Our results showed that endogenous H 2 S synthesized by CSE promotes the proliferation of AGS cells, most probably through inhibition of apoptosis.…”

mentioning

confidence: 99%

Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells

Sekiguchi

Sekimoto

Ogura

et al. 2016

Biological & Pharmaceutical Bulletin

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Hydrogen sulfide (H 2 S), the third gasotransmitter, is endogenously generated by certain H 2 S synthesizing enzymes, including cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) from L-cysteine in the mammalian body. Several studies have shown that endogenous and exogenous H 2 S affects the proliferation of cancer cells, although the effects of H 2 S appear to vary with cell type, being either promotive or suppressive. In the present study, we determined whether endogenously formed H 2 S regulates proliferation in human gastric cancer AGS cells. CSE, but not CBS, was expressed in AGS cells. CSE inhibitors, DL-propargylglycine (PPG) and β-cyano-L-alanine (BCA), significantly suppressed the proliferation of AGS cells in a concentration-dependent manner. CSE inhibitors did not increase lactate dehydrogenase (LDH) release in the same concentration range. The inhibitory effects of PPG and BCA on cell proliferation were reversed by repetitive application of NaHS, a donor of H 2 S. Interestingly, nuclear condensation and fragmentation were detected in AGS cells treated with PPG or BCA. These results suggest that endogenous H 2 S produced by CSE may contribute to the proliferation of gastric cancer AGS cells, most probably through anti-apoptotic actions.

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H2S Donor, S-Propargyl-Cysteine, Increases CSE in SGC-7901 and Cancer-Induced Mice: Evidence for a Novel Anti-Cancer Effect of Endogenous H2S?

Cited by 97 publications

References 31 publications

Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways

Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways

The Therapeutic Potential of Cystathionine β-Synthetase/Hydrogen Sulfide Inhibition in Cancer

Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells

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