Galangin inhibits cell invasion by suppressing the epithelial-mesenchymal transition and inducing apoptosis in renal cell carcinoma

Cao,Jingyi; Wang,Hainan; Chen,Feifei; Fang,Jianzheng; Xu,Aiming; Xi,Wei; Zhang,Shengli; Wu,Gang; Wang,Zengjun

doi:10.3892/mmr.2016.5042

Galangin inhibits cell invasion by suppressing the epithelial-mesenchymal transition and inducing apoptosis in renal cell carcinoma

Authors:
- Jingyi Cao
- Hainan Wang
- Feifei Chen
- Jianzheng Fang
- Aiming Xu
- Wei Xi
- Shengli Zhang
- Gang Wu
- Zengjun Wang
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Affiliations: State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Urology, Xuzhou Third People's Hospital, Xuzhou, Jiangsu 221005, P.R. China
Published online on: March 24, 2016 https://doi.org/10.3892/mmr.2016.5042
Pages: 4238-4244
Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Galangin, a flavonoid extracted from the root of the Alpinia officinarum Hence, has been shown to have anticancer properties against several types of cancer cells. However, the influence of galangin on human renal cancer cells remains to be elucidated. In the present study, proliferation of 786‑0 and Caki‑1 cells was suppressed following exposure to various doses of galangin. Cell invasion and wound healing assays were used to observe the effect of galangin on invasion and migration. The results demonstrated that Galangin inhibited cell invasion by suppressing the epithelial mesenchymal transition (EMT), with an increase in the expression of E‑cadherin and decreased expression levels of N‑cadherin and vimentin. The apoptosis induced by galangin was analyzed by flow cytometry. The results revealed that galangin induced apoptosis in a dose‑dependent manner. The accumulation of reactive oxygen species (ROS) is an important contributing factor for the apoptosis of various types of cancer cell. The dichlorofluorescein-diacetate method was used to determine the level of ROS. Galangin induced the accumulation of intracellular ROS and malondialdehyde, and decreased the activities of total antioxidant and superoxide dismutase in renal cell carcinoma cells. Galangin exerted an antiproliferative effect and inhibited renal cell carcinoma invasion by suppressing the EMT. This treatment also induced apoptosis, accompanied by the production of ROS. Therefore, the present data suggested that galangin may have beneficial effects by preventing renal cell carcinoma growth, inhibiting cell invasion via the EMT and inducing cell apoptosis.

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1	Chow WH, Devesa SS, Warren JL and Fraumeni JF Jr: Rising incidence of renal cell cancer in the United States. JAMA. 281:1628–1631. 1999. View Article : Google Scholar : PubMed/NCBI
2	Gupta K, Miller JD, Li JZ, Russell MW and Charbonneau C: Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): A literature review. Cancer Treat Rev. 34:193–205. 2008. View Article : Google Scholar : PubMed/NCBI
3	Hollingsworth JM, Miller DC, Daignault S and Hollenbeck BK: Five-year survival after surgical treatment for kidney cancer: A population-based competing risk analysis. Cancer. 109:1763–1768. 2007. View Article : Google Scholar : PubMed/NCBI
4	Hunt JD, van der Hel OL, McMillan GP, Boffetta P and Brennan P: Renal cell carcinoma in relation to cigarette smoking: Meta-analysis of 24 studies. Int J Cancer. 114:101–108. 2005. View Article : Google Scholar
5	Yuan JM, Castelao JE, Gago-Dominguez M, Yu MC and Ross RK: Tobacco use in relation to renal cell carcinoma. Cancer Epidemiol Biomarkers Prev. 7:429–433. 1998.PubMed/NCBI
6	Bjørge Tand Tretli S and Engeland A: Relation of height and body mass index to renal cell carcinoma in two million Norwegian men and women. Am J Epidemiol. 160:1168–1176. 2004. View Article : Google Scholar
7	van Dijk BA, Schouten LJ, Kiemeney LA, Goldbohm RA and van den Brandt PA: Relation of height, body mass, energy intake and physical activity to risk of renal cell carcinoma: Results from the Netherlands cohort study. Am J Epidemiol. 160:1159–1167. 2004. View Article : Google Scholar : PubMed/NCBI
8	McLaughlin JK, Chow WH, Mandel JS, Mellemgaard A, McCredie M, Lindblad P, Schlehofer B, Pommer W, Niwa S and Adami HO: International renal-cell cancer study. VIII. Role of diuretics, other anti-hypertensive medications and hypertension. Int J Cancer. 63:216–221. 1995. View Article : Google Scholar : PubMed/NCBI
9	McCredie M, Pommer W, McLaughlin JK, Stewart JH, Lindblad P, Mandel JS, Mellemgaard A, Schlehofer B and Niwa S: International renal-cell cancer study. II. Analgesics. Int J Cancer. 60:345–349. 1995. View Article : Google Scholar : PubMed/NCBI
10	McDermott DF: Immunotherapy of metastatic renal cell carcinoma. Cancer. 115(Suppl 10): 2298–2305. 2009. View Article : Google Scholar : PubMed/NCBI
11	Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, et al: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 356:125–134. 2007. View Article : Google Scholar : PubMed/NCBI
12	Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, et al: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 356:115–124. 2007. View Article : Google Scholar : PubMed/NCBI
13	Zhang HT, Luo H, Wu J, Lan LB, Fan DH, Zhu KD, Chen XY, Wen M and Liu HM: Galangin induces apoptosis of hepatocellular carcinoma cells via the mitochondrial pathway. World J Gastroenterol. 16:3377–3384. 2010. View Article : Google Scholar : PubMed/NCBI
14	Capasso R and Mascolo N: Inhibitory effect of the plant flavonoid galangin on rat vas deferens in vitro. Life Sci. 72:2993–3001. 2003. View Article : Google Scholar : PubMed/NCBI
15	Kim DA, Jeon YK and Nam MJ: Galangin induces apoptosis in gastric cancer cells via regulation of ubiquitin carboxy-terminal hydrolase isozyme L1 and glutathione S-transferase P. Food Chem Toxicol. 50:684–688. 2012. View Article : Google Scholar
16	Zhang W, Tang B, Huang Q and Hua Z: Galangin inhibits tumor growth and metastasis of B16F10 melanoma. J Cell Biochem. 114:152–161. 2013. View Article : Google Scholar
17	Heo MY, Sohn SJ and Au WW: Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate. Mutat Res. 488:135–150. 2001. View Article : Google Scholar : PubMed/NCBI
18	Thiery JP and Sleeman JP: Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 7:131–142. 2006. View Article : Google Scholar : PubMed/NCBI
19	Shi J, Wang DM, Wang CM, Hu Y, Liu AH, Zhang YL, Sun B and Song JG: Insulin receptor substrate-1 suppresses transforming growth factor-beta1-mediated epithelial-mesenchymal transition. Cancer Res. 69:7180–7187. 2009. View Article : Google Scholar : PubMed/NCBI
20	Fan F, Samuel S, Evans KW, Lu J, Xia L, Zhou Y, Sceusi E, Tozzi F, Ye XC, Mani SA and Ellis LM: Overexpression of snail induces epithelial-mesenchymal transition and a cancer stem cell-like phenotype in human colorectal cancer cells. Cancer Med. 1:5–16. 2012. View Article : Google Scholar
21	Saito RA, Watabe T, Horiguchi K, Kohyama T, Saitoh M, Nagase T and Miyazono K: Thyroid transcription factor-1 inhibits transforming growth factor-beta-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells. Cancer Res. 69:2783–2791. 2009. View Article : Google Scholar : PubMed/NCBI
22	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI
23	Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI
24	El-Najjar N, Chatila M, Moukadem H, Vuorela H, Ocker M, Gandesiri M, Schneider-Stock R and Gali-Muhtasib H: Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling. Apoptosis. 15:183–195. 2010. View Article : Google Scholar
25	Circu ML and Aw TY: Reactive oxygen species, cellular redox systems and apoptosis. Free Radic Biol Med. 48:749–762. 2010. View Article : Google Scholar : PubMed/NCBI
26	Gamaley IA and Klyubin IV: Roles of reactive oxygen species: Signaling and regulation of cellular functions. Int Rev Cytol. 188:203–255. 1999. View Article : Google Scholar : PubMed/NCBI
27	Parhiz H, Roohbakhsh A, Soltani F, Rezaee R and Iranshahi M: Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res. 29:323–31. 2015. View Article : Google Scholar
28	Agati G, Azzarello E, Pollastri S and Tattini M: Flavonoids as antioxidants in plants: location and functional significance. Plant Sci. 2012 Nov;196:67–76. View Article : Google Scholar : PubMed/NCBI