Sulforaphane-cysteine suppresses invasion via downregulation of galectin-1 in human prostate cancer DU145 and PC3 cells

Tian,Hua; Zhou,Yan; Yang,Gaoxiang; Geng,Yang; Wu,Sai; Hu,Yabin; Lin,Kai; Wu,Wei

doi:10.3892/or.2016.4942

Sulforaphane-cysteine suppresses invasion via downregulation of galectin-1 in human prostate cancer DU145 and PC3 cells

Authors:
- Hua Tian
- Yan Zhou
- Gaoxiang Yang
- Yang Geng
- Sai Wu
- Yabin Hu
- Kai Lin
- Wei Wu
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Affiliations: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China
Published online on: July 15, 2016 https://doi.org/10.3892/or.2016.4942
Pages: 1361-1368

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Abstract

Our previous study showed that sulforaphane (SFN) inhibits invasion in human prostate cancer DU145 cells; however, the underlying mechanisms were not profoundly investigated. In the present study, we found that sulforaphane-cysteine (SFN-Cys), as a metabolite of SFN, inhibits invasion and possesses a novel mechanism in prostate cancer DU145 and PC3 cells. The scratch and Transwell assays showed that SFN-Cys (15 µM) inhibited both migration and invasion, with cell morphological changes, such as cell shrinkage and pseudopodia shortening. The cell proliferation (MTS) assay indicated that cell viability was markedly suppressed with increasing concentrations of SFN‑Cys. Furthermore, the Transwell assay showed that inhibition of SFN‑Cys‑triggered invasion was tightly linked to the sustained extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Western blot analysis revealed that SFN-Cys downregulated galectin-1 protein, an invasion‑related protein, and that the galectin‑1 reduction could be blocked by ERK1/2 inhibitor PD98059 (25 µM). Moreover, immunofluorescence staining showed that the expression level of galectin-1 protein was significantly reduced in the cells treated with SFN‑Cys. Hence, SFN‑Cys‑inhibited invasion resulted from the sustained ERK1/2 phosphorylation and ERK1/2‑triggered galectin-1 downregulation, suggesting that galectin-1 is a new SFN-Cys target inhibiting invasion apart from ERK1/2, in the treatment of prostate cancer.

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1	Abdull Razis AF and Noor NM: Cruciferous vegetables: Dietary phytochemicals for cancer prevention. Asian Pac J Cancer Prev. 14:1565–1570. 2013. View Article : Google Scholar : PubMed/NCBI
2	Lenzi M, Fimognari C and Hrelia P: Sulforaphane as a promising molecule for fighting cancer. Cancer Treat Res. 159:207–223. 2014. View Article : Google Scholar
3	Clarke JD, Hsu A, Williams DE, Dashwood RH, Stevens JF, Yamamoto M and Ho E: Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice. Pharm Res. 28:3171–3179. 2011. View Article : Google Scholar : PubMed/NCBI
4	Myzak MC, Karplus PA, Chung FL and Dashwood RH: A novel mechanism of chemoprotection by sulforaphane: Inhibition of histone deacetylase. Cancer Res. 64:5767–5774. 2004. View Article : Google Scholar : PubMed/NCBI
5	Gasper AV, Al-Janobi A, Smith JA, Bacon JR, Fortun P, Atherton C, Taylor MA, Hawkey CJ, Barrett DA and Mithen RF: Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am J Clin Nutr. 82:1283–1291. 2005.PubMed/NCBI
6	Peng X, Zhou Y, Tian H, Yang G, Li C, Geng Y, Wu S and Wu W: Sulforaphane inhibits invasion by phosphorylating ERK1/2 to regulate E-cadherin and CD44v6 in human prostate cancer DU145 cells. Oncol Rep. 34:1565–1572. 2015.PubMed/NCBI
7	Futran AS, Link AJ, Seger R and Shvartsman SY: ERK as a model for systems biology of enzyme kinetics in cells. Curr Biol. 23:R972–R979. 2013. View Article : Google Scholar : PubMed/NCBI
8	Goulet AC, Chigbrow M, Frisk P and Nelson MA: Selenomethionine induces sustained ERK phosphorylation leading to cell-cycle arrest in human colon cancer cells. Carcinogenesis. 26:109–117. 2005. View Article : Google Scholar
9	Krishna-Subramanian S, Hanski ML, Loddenkemper C, Choudhary B, Pagès G, Zeitz M and Hanski C: UDCA slows down intestinal cell proliferation by inducing high and sustained ERK phosphorylation. Int J Cancer. 130:2771–2782. 2012. View Article : Google Scholar
10	Li C, Zhou Y, Peng X, Du L, Tian H, Yang G, Niu J and Wu W: Sulforaphane inhibits invasion via activating ERK1/2 signaling in human glioblastoma U87MG and U373MG cells. PLoS One. 9:e905202014. View Article : Google Scholar : PubMed/NCBI
11	Yang TY, Chang GC, Chen KC, Hung HW, Hsu KH, Sheu GT and Hsu SL: Sustained activation of ERK and Cdk2/cyclin-A signaling pathway by pemetrexed leading to S-phase arrest and apoptosis in human non-small cell lung cancer A549 cells. Eur J Pharmacol. 663:17–26. 2011. View Article : Google Scholar : PubMed/NCBI
12	Thomas W, Coen N, Faherty S, Flatharta CO and Harvey BJ: Estrogen induces phospholipase A2 activation through ERK1/2 to mobilize intracellular calcium in MCF-7 cells. Steroids. 71:256–265. 2006. View Article : Google Scholar
13	Liu Z, Yu X and Shaikh ZA: Rapid activation of ERK1/2 and AKT in human breast cancer cells by cadmium. Toxicol Appl Pharmacol. 228:286–294. 2008. View Article : Google Scholar : PubMed/NCBI
14	Bacigalupo ML, Manzi M, Rabinovich GA and Troncoso MF: Hierarchical and selective roles of galectins in hepatocarcinogenesis, liver fibrosis and inflammation of hepatocellular carcinoma. World J Gastroenterol. 19:8831–8849. 2013. View Article : Google Scholar :
15	Tang D, Zhang J, Yuan Z, Gao J, Wang S, Ye N, Li P, Gao S, Miao Y, Wang D, et al: Pancreatic satellite cells derived galectin-1 increase the progression and less survival of pancreatic ductal adenocarcinoma. PLoS One. 9:e904762014. View Article : Google Scholar : PubMed/NCBI
16	Wu MH, Hong HC, Hong TM, Chiang WF, Jin YT and Chen YL: Targeting galectin-1 in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis by downregulating MCP-1/CCL2 expression. Clin Cancer Res. 17:1306–1316. 2011. View Article : Google Scholar : PubMed/NCBI
17	Kohrenhagen N, Voelker HU, Kapp M, Dietl J and Kämmerer U: The expression of galectin-1 in vulvar neoplasia. Anticancer Res. 30:1547–1552. 2010.PubMed/NCBI
18	Barrow H, Rhodes JM and Yu LG: The role of galectins in colorectal cancer progression. Int J Cancer. 129:1–8. 2011. View Article : Google Scholar : PubMed/NCBI
19	Wu MH, Hong TM, Cheng HW, Pan SH, Liang YR, Hong HC, Chiang WF, Wong TY, Shieh DB, Shiau AL, et al: galectin-1-mediated tumor invasion and metastasis, upregulated matrix metalloproteinase expression, and reorganized actin cytoskeletons. Mol Cancer Res. 7:311–318. 2009. View Article : Google Scholar : PubMed/NCBI
20	Elola MT, Wolfenstein-Todel C, Troncoso MF, Vasta GR and Rabinovich GA: Galectins: Matricellular glycan-binding proteins linking cell adhesion, migration, and survival. Cell Mol Life Sci. 64:1679–1700. 2007. View Article : Google Scholar : PubMed/NCBI
21	Fuertes MB, Molinero LL, Toscano MA, Ilarregui JM, Rubinstein N, Fainboim L, Zwirner NW and Rabinovich GA: Regulated expression of galectin-1 during T-cell activation involves Lck and Fyn kinases and signaling through MEK1/ERK, p38 MAP kinase and p70S6 kinase. Mol Cell Biochem. 267:177–185. 2004. View Article : Google Scholar
22	Wang L, Tian Z, Yang Q, Li H, Guan H, Shi B, Hou P and Ji M: Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway. Oncotarget. 6:25917–25931. 2015. View Article : Google Scholar : PubMed/NCBI
23	Mokhtari RB, Kumar S, Islam SS, Yazdanpanah M, Adeli K, Cutz E and Yeger H: Combination of carbonic anhydrase inhibitor, acetazolamide, and sulforaphane, reduces the viability and growth of bronchial carcinoid cell lines. BMC Cancer. 13:3782013. View Article : Google Scholar : PubMed/NCBI
24	Pastorek M, Simko V, Takacova M, Barathova M, Bartosova M, Hunakova L, Sedlakova O, Hudecova S, Krizanova O, Dequiedt F, et al: Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy. Int J Oncol. 47:51–60. 2015.PubMed/NCBI
25	Deschênes-Simard X, Gaumont-Leclerc MF, Bourdeau V, Lessard F, Moiseeva O, Forest V, Igelmann S, Mallette FA, Saba-El-Leil MK, Meloche S, et al: Tumor suppressor activity of the ERK/MAPK pathway by promoting selective protein degradation. Genes Dev. 27:900–915. 2013. View Article : Google Scholar : PubMed/NCBI
26	Fulcher JA, Hashimi ST, Levroney EL, Pang M, Gurney KB, Baum LG and Lee B: galectin-1-matured human mono-cyte-derived dendritic cells have enhanced migration through extracellular matrix. J Immunol. 177:216–226. 2006. View Article : Google Scholar : PubMed/NCBI
27	Kim HJ, Do IG, Jeon HK, Cho YJ, Park YA, Choi JJ, Sung CO, Lee YY, Choi CH, Kim TJ, et al: Galectin 1 expression is associated with tumor invasion and metastasis in stage IB to IIA cervical cancer. Hum Pathol. 44:62–68. 2013. View Article : Google Scholar
28	Chen J, Zhou SJ, Zhang Y, Zhang GQ, Zha TZ, Feng YZ and Zhang K: Clinicopathological and prognostic significance of galectin-1 and vascular endothelial growth factor expression in gastric cancer. World J Gastroenterol. 19:2073–2079. 2013. View Article : Google Scholar : PubMed/NCBI
29	Zhao XY, Chen TT, Xia L, Guo M, Xu Y, Yue F, Jiang Y, Chen GQ and Zhao KW: Hypoxia inducible factor-1 mediates expression of galectin-1: The potential role in migration/invasion of colorectal cancer cells. Carcinogenesis. 31:1367–1375. 2010. View Article : Google Scholar : PubMed/NCBI
30	Juszczynski P, Ouyang J, Monti S, Rodig SJ, Takeyama K, Abramson J, Chen W, Kutok JL, Rabinovich GA and Shipp MA: The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma. Proc Natl Acad Sci USA. 104:13134–13139. 2007. View Article : Google Scholar : PubMed/NCBI
31	Yoon S and Seger R: The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions. Growth Factors. 24:21–44. 2006. View Article : Google Scholar : PubMed/NCBI
32	Hsieh YS, Chu SC, Yang SF, Chen PN, Liu YC and Lu KH: Silibinin suppresses human osteosarcoma MG-63 cell invasion by inhibiting the ERK-dependent c-Jun/AP-1 induction of MMP-2. Carcinogenesis. 28:977–987. 2007. View Article : Google Scholar
33	Barondes SH, Cooper DN, Gitt MA and Leffler H: galectins. Structure and function of a large family of animal lectins. J Biol Chem. 269:20807–20810. 1994.PubMed/NCBI
34	Yun SP, Lee SJ, Jung YH and Han HJ: galectin-1 stimulates motility of human umbilical cord blood-derived mesenchymal stem cells by downregulation of smad2/3-dependent collagen 3/5 and upregulation of NF-κB-dependent fibronectin/laminin 5 expression. Cell Death Dis. 5:e10492014. View Article : Google Scholar
35	Rizqiawan A, Tobiume K, Okui G, Yamamoto K, Shigeishi H, Ono S, Shimasue H, Takechi M, Higashikawa K and Kamata N: Autocrine galectin-1 promotes collective cell migration of squamous cell carcinoma cells through up-regulation of distinct integrins. Biochem Biophys Res Commun. 441:904–910. 2013. View Article : Google Scholar : PubMed/NCBI
36	Etulain J, Negrotto S, Tribulatti MV, Croci DO, Carabelli J, Campetella O, Rabinovich GA and Schattner M: Control of angiogenesis by galectins involves the release of platelet-derived proangiogenic factors. PLoS One. 9:e964022014. View Article : Google Scholar : PubMed/NCBI
37	Le Mercier M, Lefranc F, Mijatovic T, Debeir O, Haibe-Kains B, Bontempi G, Decaestecker C, Kiss R and Mathieu V: Evidence of galectin-1 involvement in glioma chemoresistance. Toxicol Appl Pharmacol. 229:172–183. 2008. View Article : Google Scholar : PubMed/NCBI