Sodium/calcium exchanger is involved in apoptosis induced by H2S in tumor cells through decreased levels of intracellular pH

Szadvári, Ivan; Hudecová, Soňa; Chovancova, Barbora; Matúšková, Miroslava; Cholujová, Dana; Lencesova, Lubomira; Valerian, David; Ondriaš, Karol; Babula, Petr; Križanová, Oľga

doi:10.1016/j.niox.2019.02.011

Cited by 27 publications

(25 citation statements)

References 37 publications

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“…H 2 S donors were also shown to relieve visceral pain [133][134][135] and an HS-trimebutine is now in Phase II clinical trials as an abdominal analgesic (NCT01926444). The role of H 2 S has also been investigated in the etiology of cancer and diabetes, however, the studies show contradictory results [136][137][138][139][140][141][142][143][144][145][146][147]…”

Section: Other Effects Of H 2 Smentioning

confidence: 99%

Hydrogen Sulfide in Pharmacotherapy, Beyond the Hydrogen Sulfide-Donors

et al. 2020

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Hydrogen sulfide (H2S) is one of the important biological mediators involved in physiological and pathological processes in mammals. Recently developed H2S donors show promising effects against several pathological processes in preclinical and early clinical studies. For example, H2S donors have been found to be effective in the prevention of gastrointestinal ulcers during anti-inflammatory treatment. Notably, there are well-established medicines used for the treatment of a variety of diseases, whose chemical structure contains sulfur moieties and may release H2S. Hence, the therapeutic effect of these drugs may be partly the result of the release of H2S occurring during drug metabolism and/or the effect of these drugs on the production of endogenous hydrogen sulfide. In this work, we review data regarding sulfur drugs commonly used in clinical practice that can support the hypothesis about H2S-dependent pharmacotherapeutic effects of these drugs.

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Section: Other Effects Of H 2 Smentioning

confidence: 99%

Hydrogen Sulfide in Pharmacotherapy, Beyond the Hydrogen Sulfide-Donors

et al. 2020

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“…GYY4137 is a slow sul de donor that release H 2 S slowly and steadily, either in aqueous solution or administered to the animals, because of low toxicity [31]. Effect of GYY4137 on tumor suppression was already demonstrated on DLD1 and HepG2 cells [13,14]. In cell cultures, DLDx exhibited also increased proliferation compared to DLD1 and GYY4137 signi cantly decreased this process in DLDx cells, but not in DLD1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Speci cally, endogenous H 2 S or a relatively low level of exogenous H 2 S may exhibit a pro-cancer effect, whereas exposure to H 2 S at a higher amount or for a long period may lead to cancer cell death [12]. In favor of this hypothesis might be a fact, that slow sul de donor GYY4137 can induce apoptosis in stable cancer cell lines in vitro, but also in xenografts induced in immunode cient mice treated with GYY4137 [13,14].…”

Section: Introductionmentioning

confidence: 99%

Cystathionine-β-synthase affects organization of cytoskeleton and modulates carcinogenesis in colorectal carcinoma cells

Lišková

Chovancova

Babula

et al. 2020

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Background: Cystathionine-b-synthase (CBS), one of three enzymes that endogenously produce hydrogen sulfide, is extensively studied for its relevance also in various tumor’s cell. In our previous work we observed that immunofluorescence pattern of CBS is very similar to that from tubulin and actin. Therefore, we focused on potential interaction of CBS with cytoskeletal proteins b-actin and b-tubulin and functional relevance of the potential interaction of these proteins in colorectal carcinoma cell lines.Methods: To study potential interaction of CBS with cytoskeletal proteins and its functional consequences, CBS-knockout DLD1 (DLDx) cell line was established by using the CRISPR/Cas9 gene editing method. Interaction of selected cytoskeletal protein with CBS was studied by immunoprecipitation and Western blot analysis, immunofluorescence and proximity ligation assay. Functional consequences were studied by proliferation and migration assays and by generation of xenografts in SCID/bg mice.Results: We have found that CBS, an enzyme that endogenously produces H2S, binds to cytoskeletal b-tubulin and to lesser extent also to b-actin in colorectal carcinoma derived cells. When CBS was knockouted by CRISPR/Cas9 technique (DLDx), we observed de-arranged cytoskeleton compared to unmodified DLD1 cell line. Treatment of these cells with a slow sulfide donor GYY4137 resulted in normal organization of cytoskeleton, thus pointing to the role of CBS in microtubule dynamics. To evaluate the physiological importance of this observation, both DLD1 and DLDx cells were injected into SCID/bg mice and size/mass of developed xenografts was evaluated. Significantly larger tumors developed from DLDx compared to DLD1 cells, which correlated with increased proliferation of these cells. Conclusions: Taken together, in colorectal cancer DLD1 cells, CBS binds to cytoskeleton, modulates microtubule dynamics and thus affects the proliferation and migration in colorectal carcinoma stable cell line.

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“…The treatment with GYY4137 elevates the expressions of apoptotic markers caspase-9 and cleaved PARP in breast cancer MCF-7 cells, colorectal cancer Caco-2 cells [15], and ovarian cancer A2780 cells [150], with little or no effects in normal cell lines IMR90 cells [14] and Ea. hy926 [150]. STAT-3 pathway plays a crucial role in inducing apoptosis, and blocking this pathway is associated with improved apoptotic activities in different cancer types including lung cancer [149], pancreatic cancer [151], and HCC [152].…”

Section: H 2 S Donor Induces Apoptosismentioning

confidence: 98%

“…H2S donors regulate apoptosis in cancer cells by interacting with numerous apoptosis-inducing pathways [15,149]. The treatment with GYY4137 elevates the expressions of apoptotic markers caspase-9 and cleaved PARP in breast cancer MCF-7 cells, colorectal cancer Caco-2 cells [15], and ovarian cancer A2780 cells [150], with little or no effects in normal cell lines IMR90 cells [14] and Ea. hy926 [150].…”

Section: H 2 S Donor Induces Apoptosismentioning

confidence: 99%

Role of hydrogen sulfide donors in cancer development and progression

et al. 2021

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In recent years, a vast number of potential cancer therapeutic targets have emerged. However, developing efficient and effective drugs for the targets is of major concern. Hydrogen sulfide (H2S), one of the three known gasotransmitters, is involved in the regulation of various cellular activities such as autophagy, apoptosis, migration, and proliferation. Low production of H2S has been identified in numerous cancer types. Treating cancer cells with H2S donors is the common experimental technique used to improve H2S levels; however, the outcome depends on the concentration/dose, time, cell type, and sometimes the drug used. Both natural and synthesized donors are available for this purpose, although their effects vary independently ranging from strong cancer suppressors to promoters. Nonetheless, numerous signaling pathways have been reported to be altered following the treatments with H2S donors which suggest their potential in cancer treatment. This review will analyze the potential of H2S donors in cancer therapy by summarizing key cellular processes and mechanisms involved.

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Sodium/calcium exchanger is involved in apoptosis induced by H2S in tumor cells through decreased levels of intracellular pH

Cited by 27 publications

References 37 publications

Hydrogen Sulfide in Pharmacotherapy, Beyond the Hydrogen Sulfide-Donors

Hydrogen Sulfide in Pharmacotherapy, Beyond the Hydrogen Sulfide-Donors

Cystathionine-β-synthase affects organization of cytoskeleton and modulates carcinogenesis in colorectal carcinoma cells

Role of hydrogen sulfide donors in cancer development and progression

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