Endogenous H2S producing enzymes are involved in apoptosis induction in clear cell renal cell carcinoma

BREZA, Jan, Andrea SOLTYSOVA, Sona HUDECOVA, Adela PENESOVA, Ivan SZADVÁRI, Petr BABULA, Barbora CHOVANCOVA, Lubomira LENCESOVA, Ondrej POS, Jan BREZA, Karol ONDRIAS and Oľga KRIŽANOVÁ. Endogenous H2S producing enzymes are involved in apoptosis induction in clear cell renal cell carcinoma. BMC Cancer. London: BioMed Central, 2018, vol. 18, No 591, p. 1-8. ISSN 1471-2407. Available from: https://dx.doi.org/10.1186/s12885-018-4508-1.

Basic information

• Original name: Endogenous H2S producing enzymes are involved in apoptosis induction in clear cell renal cell carcinoma
• Authors: BREZA, Jan (703 Slovakia), Andrea SOLTYSOVA (703 Slovakia), Sona HUDECOVA (703 Slovakia), Adela PENESOVA (703 Slovakia), Ivan SZADVÁRI (703 Slovakia, belonging to the institution), Petr BABULA (203 Czech Republic, belonging to the institution), Barbora CHOVANCOVA (703 Slovakia), Lubomira LENCESOVA (703 Slovakia), Ondrej POS (703 Slovakia), Jan BREZA (703 Slovakia), Karol ONDRIAS (703 Slovakia) and Oľga KRIŽANOVÁ (703 Slovakia, guarantor, belonging to the institution).
• Edition: BMC Cancer, London, BioMed Central, 2018, 1471-2407.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30105 Physiology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 2.933
• RIV identification code: RIV/00216224:14110/18:00104139
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1186/s12885-018-4508-1
• UT WoS: 000433334000005
• Keywords in English: Cystathionine-beta-synthase; Cystathionine gamma-lyase; 3-Mercaptopyruvate sulfurtransferase; Apoptosis; Clear cell renal cell carcinoma
• Tags: 14110515, rivok
• Tags: International impact, Reviewed

Abstract

Background: Knowledge about the expression and thus a role of enzymes that produce endogenous H2S-cystathionine-beta-synthase, cystathionine gamma-lyase and mercaptopyruvate sulfurtransferase - in renal tumors is still controversial. In this study we aimed to determine the expression of these enzymes relatively to the expression in unaffected part of kidney from the same patient and to found relation of these changes to apoptosis. To evaluate patient's samples, microarray and immunohistochemistry was used. Methods: To determine the physiological importance, we used RCC4 stable cell line derived from clear cell renal cell carcinoma, where apoptosis induction by a mixture of five chemotherapeutics with/without silencing of H2S-producing enzymes was detected. Immunofluorescence was used to determine each enzyme in the cells. Results: In clear cell renal cell carcinomas, expression of H2S-producing enzymes was mostly decreased compared to a part of kidney that was distal from the tumor. To evaluate a potential role of H2S-producing enzymes in the apoptosis induction, we used RCC4 stable cell line. We have found that silencing of cystathionine-beta-synthase and cystathionine.-lyase prevented induction of apoptosis. Immunofluorescence staining clearly showed that these enzymes were upregulated during apoptosis in RCC4 cells. Conclusion: Based on these results we concluded that in clear cell renal cell carcinoma, reduced expression of the H2S-producing enzymes, mainly cystathionine gamma-lyase, might contribute to a resistance to the induction of apoptosis. Increased production of the endogenous H2S, or donation from the external sources might be of a therapeutic importance in these tumors.