Exogenous hydrogen sulfide exerts proliferation, anti-apoptosis, angiopoiesis and migration effects via activating HSP90 pathway in EC109 cells

Lei,Yiyan; Zhen,Yulan; Zhang,Wei; Sun,Xiuting; Lin,Xiaoxiong; Feng,Jianqiang; Luo,Honghe; Chen,Zhenguang; Su,Chunhua; Zeng,Bo; Chen,Jingfu

doi:10.3892/or.2016.4734

Exogenous hydrogen sulfide exerts proliferation, anti-apoptosis, angiopoiesis and migration effects via activating HSP90 pathway in EC109 cells

Authors:
- Yiyan Lei
- Yulan Zhen
- Wei Zhang
- Xiuting Sun
- Xiaoxiong Lin
- Jianqiang Feng
- Honghe Luo
- Zhenguang Chen
- Chunhua Su
- Bo Zeng
- Jingfu Chen
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Affiliations: Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangdong, Guangzhou 510080, P.R. China, Department of Oncology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China, Department of Cardiovasology and Cardiac Care Unit (CCU), Huangpu Division of The First Affiliated Hospital, Sun Yat-sen University, Guangdong, Guangzhou 510700, P.R. China, Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, P.R. China
Published online on: April 5, 2016 https://doi.org/10.3892/or.2016.4734
Pages: 3714-3720

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Abstract

Hydrogen sulfide (H2S) participates in diverse physiological and pathophysiologic processes of cancer both in vitro and in vivo. We have previously reported the proliferation/anti-apoptosis/angiogenesis/migration effects of exogenous H2S on liver cancer and glioma via amplifying the activation of NF-κB and p38 MAPK/ERK1/2-COX-2 pathway. However, the effects of H2S on EC109 esophageal cells remain unclear. The present study demonstrated the effects of exogenous H2S on cancer cell growth via activating HSP90 pathways in EC109 esophageal cells. EC109 esophageal cells were treated with 400 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of HSP90, bcl-2, caspase-3, bax and MMP-2 were detected by western blot assay. Cell viability was detected by Cell Counting Kit-8 (CCK-8). The migration rate was analyzed using a Transwell migration assay and ImageJ software. NaHS promoted cell proliferation, as evidenced by an increase in cell viability. In addition, NaHS treatment reduced apoptosis, as indicated by the increased bcl-2 expression and decreased cleaved caspase-3 and bax expression. Importantly, exposure of NaHS increased the expression of MMP-2, the migration rate and expression of VEGF. Notably, co-treatment of EC109 cells with NaHS and GA (an inhibitor of HSP90 pathway) largely suppressed the aforementioned NaHS-induced effects. The findings of the present study provided novel evidence that HSP90 pathway was involved in NaHS-induced cancer cell proliferation, anti-apoptosis, angiopoiesis and migration in EC109 esophageal cells.

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1	Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar : PubMed/NCBI
2	Wheeler JB and Reed CE: Epidemiology of esophageal cancer. Surg Clin North Am. 92:1077–1087. 2012. View Article : Google Scholar : PubMed/NCBI
3	Hongo M, Nagasaki Y and Shoji T: Epidemiology of esophageal cancer: Orient to Occident. Effects of chronology, geography and ethnicity. J Gastroenterol Hepatol. 24:729–735. 2009. View Article : Google Scholar : PubMed/NCBI
4	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar
5	Kaneko K, Kumekawa Y, Makino R, Nozawa H, Hirayama Y, Kogo M, Konishi K, Katagiri A, Kubota Y, Muramoto T, et al: EGFR gene alterations as a prognostic biomarker in advanced esophageal squamous cell carcinoma. Front Biosci. 15:65–72. 2010. View Article : Google Scholar
6	Delektorskaya VV, Chemeris GY, Zavalishina LE, Ryazantseva AA, Grigorchuk AY, Kononets PV and Davydov MI: Squamous cell carcinoma of the esophagus: Evaluation of the status of epidermal growth factor receptors (EGFR and HER-2) by immunohistochemistry and in situ hybridization. Bull Exp Biol Med. 149:615–620. 2010. View Article : Google Scholar : PubMed/NCBI
7	Berg D, Wolff C, Langer R, Schuster T, Feith M, Slotta-Huspenina J, Malinowsky K and Becker KF: Discovery of new molecular subtypes in oesophageal adenocarcinoma. PLoS One. 6:e239852011. View Article : Google Scholar : PubMed/NCBI
8	Langer R, Ott K, Specht K, Becker K, Lordick F, Burian M, Herrmann K, Schrattenholz A, Cahill MA, Schwaiger M, et al: Protein expression profiling in esophageal adenocarcinoma patients indicates association of heat-shock protein 27 expression and chemotherapy response. Clin Cancer Res. 14:8279–8287. 2008. View Article : Google Scholar : PubMed/NCBI
9	Morimoto RI: Cells in stress: Transcriptional activation of heat shock genes. Science. 259:1409–1410. 1993. View Article : Google Scholar : PubMed/NCBI
10	Beere HM: 'The stress of dying': The role of heat shock proteins in the regulation of apoptosis. J Cell Sci. 117:2641–2651. 2004. View Article : Google Scholar : PubMed/NCBI
11	Mehta TA, Greenman J, Ettelaie C, Venkatasubramaniam A, Chetter IC and McCollum PT: Heat shock proteins in vascular disease - a review. Eur J Vasc Endovasc Surg. 29:395–402. 2005. View Article : Google Scholar : PubMed/NCBI
12	Cohen SM, Mukerji R, Samadi AK, Zhang X, Zhao H, Blagg BS and Cohen MS: Novel C-terminal Hsp90 inhibitor for head and neck squamous cell cancer (HNSCC) with in vivo efficacy and improved toxicity profiles compared with standard agents. Ann Surg Oncol. 19(Suppl 3): S483–S490. 2012. View Article : Google Scholar
13	Drecoll E, Nitsche U, Bauer K, Berezowska S, Slotta-Huspenina J, Rosenberg R and Langer R: Expression analysis of heat shock protein 90 (HSP90) and Her2 in colon carcinoma. Int J Colorectal Dis. 29:663–671. 2014. View Article : Google Scholar : PubMed/NCBI
14	Jego G, Hazoumé A, Seigneuric R and Garrido C: Targeting heat shock proteins in cancer. Cancer Lett. 332:275–285. 2013. View Article : Google Scholar
15	Lu X, Xiao L, Wang L and Ruden DM: Hsp90 inhibitors and drug resistance in cancer: The potential benefits of combination therapies of Hsp90 inhibitors and other anti-cancer drugs. Biochem Pharmacol. 83:995–1004. 2012. View Article : Google Scholar :
16	Den RB and Lu B: Heat shock protein 90 inhibition: Rationale and clinical potential. Ther Adv Med Oncol. 4:211–218. 2012. View Article : Google Scholar : PubMed/NCBI
17	Chehab M, Caza T, Skotnicki K, Landas S, Bratslavsky G, Mollapour M and Bourboulia D: Targeting Hsp90 in urothelial carcinoma. Oncotarget. 6:8454–8473. 2015. View Article : Google Scholar : PubMed/NCBI
18	Wang R: Two's company, three's a crowd: Can H₂S be the third endogenous gaseous transmitter? FASEB J. 16:1792–1798. 2002. View Article : Google Scholar : PubMed/NCBI
19	Kilburn KH, Thrasher JD and Gray MR: Low-level hydrogen sulfide and central nervous system dysfunction. Toxicol Ind Health. 26:387–405. 2010. View Article : Google Scholar : PubMed/NCBI
20	Guidotti TL: Hydrogen sulfide: Advances in understanding human toxicity. Int J Toxicol. 29:569–581. 2010. View Article : Google Scholar : PubMed/NCBI
21	Han YF, Huang X, Guo X, Wu YS, Liu DH, Lu HL, Kim YC and Xu WX: Evidence that endogenous hydrogen sulfide exerts an excitatory effect on gastric motility in mice. Eur J Pharmacol. 673:85–95. 2011. View Article : Google Scholar : PubMed/NCBI
22	Schicho R, Krueger D, Zeller F, Von Weyhern CW, Frieling T, Kimura H, Ishii I, De Giorgio R, Campi B and Schemann M: Hydrogen sulfide is a novel prosecretory neuromodulator in the Guinea-pig and human colon. Gastroenterology. 131:1542–1552. 2006. View Article : Google Scholar : PubMed/NCBI
23	Cai WJ, Wang MJ, Ju LH, Wang C and Zhu YC: Hydrogen sulfide induces human colon cancer cell proliferation: Role of Akt, ERK and p21. Cell Biol Int. 34:565–572. 2010. View Article : Google Scholar : PubMed/NCBI
24	Cao Q, Zhang L, Yang G, Xu C and Wang R: Butyrate-stimulated H₂S production in colon cancer cells. Antioxid Redox Signal. 12:1101–1109. 2010. View Article : Google Scholar
25	Du SX, Xiao J, Guan F, Sun LM, Wu WS, Tang H, Du JB, Tang CS and Jin HF: Predictive role of cerebrospinal fluid hydrogen sulfide in central nervous system leukemia. Chin Med J. 124:3450–3454. 2011.
26	Levine J, Ellis CJ, Furne JK, Springfield J and Levitt MD: Fecal hydrogen sulfide production in ulcerative colitis. Am J Gastroenterol. 93:83–87. 1998. View Article : Google Scholar : PubMed/NCBI
27	Pupo E, Pla AF, Avanzato D, Moccia F, Cruz JE, Tanzi F, Merlino A, Mancardi D and Munaron L: Hydrogen sulfide promotes calcium signals and migration in tumor-derived endothelial cells. Free Radic Biol Med. 51:1765–1773. 2011. View Article : Google Scholar : PubMed/NCBI
28	Rose P, Moore PK, Ming SH, Nam OC, Armstrong JS and Whiteman M: Hydrogen sulfide protects colon cancer cells from chemopreventative agent beta-phenylethyl isothiocyanate induced apoptosis. World J Gastroenterol. 11:3990–3997. 2005. View Article : Google Scholar : PubMed/NCBI
29	Szabo C, Coletta C, Chao C, Módis K, Szczesny B, Papapetropoulos A and Hellmich MR: Tumor-derived hydrogen sulfide, produced by cystathionine-β-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer. Proc Natl Acad Sci USA. 110:12474–12479. 2013. View Article : Google Scholar
30	Zhen Y, Pan W, Hu F, Wu H, Feng J, Zhang Y and Chen J: Exogenous hydrogen sulfide exerts proliferation/anti-apoptosis/angiogenesis/migration effects via amplifying the activation of NF-κB pathway in PLC/PRF/5 hepatoma cells. Int J Oncol. 46:2194–2204. 2015.PubMed/NCBI
31	Zhen Y, Zhang W, Liu C, He J, Lu Y, Guo R, Feng J, Zhang Y and Chen J: Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways. Oncol Rep. 34:2413–2422. 2015.PubMed/NCBI
32	Tan BH, Wong PT and Bian JS: Hydrogen sulfide: A novel signaling molecule in the central nervous system. Neurochem Int. 56:3–10. 2010. View Article : Google Scholar
33	Zhang X and Bian JS: Hydrogen sulfide: A neuromodulator and neuroprotectant in the central nervous system. ACS Chem Neurosci. 5:876–883. 2014. View Article : Google Scholar : PubMed/NCBI
34	Jiang JM, Zhou CF, Gao SL, Tian Y, Wang CY, Wang L, Gu HF and Tang XQ: BDNF-TrkB pathway mediates neuroprotection of hydrogen sulfide against formaldehyde-induced toxicity to PC12 cells. PLoS One. 10:e01194782015. View Article : Google Scholar : PubMed/NCBI
35	Kashfi K: Anti-cancer activity of new designer hydrogen sulfide-donating hybrids. Antioxid Redox Signal. 20:831–846. 2014. View Article : Google Scholar :
36	Ma K, Liu Y, Zhu Q, Liu CH, Duan JL, Tan BK and Zhu YZ: H₂S donor, S-propargyl-cysteine, increases CSE in SGC-7901 and cancer-induced mice: Evidence for a novel anti-cancer effect of endogenous H₂S? PLoS One. 6:e205252011. View Article : Google Scholar
37	Bir SC, Kolluru GK, McCarthy P, Shen X, Pardue S, Pattillo CB and Kevil CG: Hydrogen sulfide stimulates ischemic vascular remodeling through nitric oxide synthase and nitrite reduction activity regulating hypoxia-inducible factor-1α and vascular endothelial growth factor-dependent angiogenesis. J Am Heart Assoc. 1:e0040932012. View Article : Google Scholar
38	Holwerda KM, Burke SD, Faas MM, Zsengeller Z, Stillman IE, Kang PM, van Goor H, McCurley A, Jaffe IZ, Karumanchi SA, et al: Hydrogen sulfide attenuates sFlt1-induced hypertension and renal damage by upregulating vascular endothelial growth factor. J Am Soc Nephrol. 25:717–725. 2014. View Article : Google Scholar :
39	Köhn C, Dubrovska G, Huang Y and Gollasch M: Hydrogen sulfide: Potent regulator of vascular tone and stimulator of angiogenesis. Int J Biomed Sci. 8:81–86. 2012.
40	Polhemus DJ, Kondo K, Bhushan S, Bir SC, Kevil CG, Murohara T, Lefer DJ and Calvert JW: Hydrogen sulfide attenuates cardiac dysfunction after heart failure via induction of angiogenesis. Circ Heart Fail. 6:1077–1086. 2013. View Article : Google Scholar : PubMed/NCBI
41	Tao BB, Liu SY, Zhang CC, Fu W, Cai WJ, Wang Y, Shen Q, Wang MJ, Chen Y, Zhang LJ, et al: VEGFR2 functions as an H₂S-targeting receptor protein kinase with its novel Cys1045-Cys1024 disulfide bond serving as a specific molecular switch for hydrogen sulfide actions in vascular endothelial cells. Antioxid Redox Signal. 19:448–464. 2013. View Article : Google Scholar :
42	Leung WK, To KF, Go MY, Chan KK, Chan FK, Ng EK, Chung SC and Sung JJ: Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma. Int J Oncol. 23:1317–1322. 2003.PubMed/NCBI
43	Egeblad M and Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2:161–174. 2002. View Article : Google Scholar : PubMed/NCBI
44	Jones JL, Shaw JA, Pringle JH and Walker RA: Primary breast myoepithelial cells exert an invasion-suppressor effect on breast cancer cells via paracrine down-regulation of MMP expression in fibroblasts and tumour cells. J Pathol. 201:562–572. 2003. View Article : Google Scholar : PubMed/NCBI
45	Li C, Li F, Zhao K, Yao J, Cheng Y, Zhao L, Li Z, Lu N and Guo Q: LFG-500 inhibits the invasion of cancer cells via downregulation of PI3K/AKT/NF-κB signaling pathway. PLoS One. 9:e913322014. View Article : Google Scholar
46	Puzovic V, Brcic I, Ranogajec I and Jakic-Razumovic J: Prognostic values of ETS-1, MMP-2 and MMP-9 expression and co-expression in breast cancer patients. Neoplasma. 61:439–446. 2014. View Article : Google Scholar : PubMed/NCBI
47	Ruan M, Zhang Z, Li S, Yan M, Liu S, Yang W, Wang L and Zhang C: Activation of Toll-like receptor-9 promotes cellular migration via up-regulating MMP-2 expression in oral squamous cell carcinoma. PLoS One. 9:e927482014. View Article : Google Scholar : PubMed/NCBI