Effect of Resveratrol on Oral Cancer Cell Invasion Induced by Lysophosphatidic Acid
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor 1 and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.
Abstract
The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor 1 and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.
참고문헌 (27)
- Robinson KL, "Oropharyngeal cancer incidence and mortality in Scotland: are rates still increasing?", Oral Oncol, 39, pp.31~36 (2003)[DOI]
- 한지형, "구강암의 발생현황과 원인", 치위생과학회지, 12(5), pp.451~458 (2012), 한국치위생과학회
- Roepman P, "An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas", Nat Genet, 37, pp.182~186 (2005)[DOI]
- Mandal M, "Epithelial to mesenchymal transition in head and neck squamous carcinoma: association of Src activation with E-cadherin down-regulation, vimentin expression, and aggressive tumor features", Cancer, 112, pp.2088~2100 (2008)[DOI]
- Kopp P, "Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the 'French paradox'?", Eur J Endocrinol, 138, pp.619~620 (1998)[DOI]
- Savouret JF, "Resveratrol and cancer: a review", Biomed Pharmacother, 56, pp.84~87 (2002)[DOI]
- Gupta SC, "Chemosensitization of tumors by resveratrol", Ann N Y Acad Sci, 1215, pp.150~160 (2011)[DOI]
- Tyagi A, "Resveratrol causes Cdc2-tyr15 phosphorylation via ATM", ATR-Chk1, Carcinogenesis, pp.2005, 26[DOI]
- Yang SH, "Genome-scale analysis of resveratrol-induced gene expression profile in human ovarian cancer cells using a cDNA microarray", Int J Oncol, 22, pp.741~750 (2003)[DOI]
- 김유나, "Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA", YAP signaling axis, 2017, pp.49, 1~9[DOI]
- Seung Hwa Kim, "Resveratrol attenuates norepinephrine-induced ovarian cancer invasiveness through downregulating hTERT expression", Archives of Pharmacal Research, 39(2), pp.240~248 (2016), 대한약학회
- Kim SE, "Resveratrol induces mitochondrial apoptosis and inhibits epithelial-mesenchymal transition in oral squamous cell carcinoma cells", Nutr Cancer, 70, pp.125~135 (2018)[DOI]
- Chang CH, "Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: a key role of AMPK and Akt", mTOR signaling, 2017, pp.50, 873~882
- Baek SH, "Resveratrol inhibits STAT3 signaling pathway through the induction of SOCS-1: role in apoptosis induction and radiosensitization in head and neck tumor cells", Phytomedicine, 23, pp.566~577 (2016)[DOI]
- Yu XD, "Resveratrol inhibits oral squamous cell carcinoma through induction of apoptosis and G2", M phase cell cycle arrest, 2016, pp.37, 2871~2877
- Subramanian S, "Cost-effectiveness of oral cancer screening: results from a cluster randomized controlled trial in India", Bull World Health Organ, 87, pp.200~206 (2009)[DOI]
- 김현덕, "Factors influencing knowledge about early signs and causes of oral cancer in Korean elders", 대한구강보건학회지, 28(4), pp.570~582 (2004), 대한예방치과·구강보건학회
- 이은주, "Characterization of newly established oral cancer cell lines derived fromsix squamous cell carcinoma and two mucoepidermoid carcinoma cells", Experimental and Molecular Medicine, 37(5), pp.379~390 (2005), 생화학분자생물학회
- Ahrendt SA, "Alcohol consumption and cigarette smoking increase the frequency of p53 mutations in non-small cell lung cancer", Cancer Res, 60, pp.3155~3159 (2000)
- Balaram P, "Oral cancer in southern India: the influence of smoking, drinking, paan-chewing and oral hygiene", Int J Cancer, 98, pp.440~445 (2002)[DOI]
- Chen SJ, "Ultra-deep targeted sequencing of advanced oral squamous cell carcinoma identifies a mutation-based prognostic gene signature", Oncotarget, 6, pp.18066~18080 (2015)[DOI]
- Tamura T, "Loss of NDRG2 expression confers oral squamous cell carcinoma with enhanced metastatic potential", Cancer Res, 77, pp.2363~2374 (2017)[DOI]
- Benesch MG, "Autotaxin in the crosshairs: taking aim at cancer and other inflammatory conditions", FEBS Lett, 588, pp.2712~2727 (2014)[DOI]
- Brusevold IJ, "Role of LPAR3, PKC and EGFR in LPA-induced cell migration in oral squamous carcinoma cells", BMC Cancer, 14, pp.432~ (2014)[DOI]
- 조경화, "Lysophosphatidic Acid-Induced TWIST1 and Slug Expression in Oral Cancer Cell Invasion", 치위생과학회지, 17(5), pp.433~438 (2017), 한국치위생과학회[DOI]
- Shan Z, "Effects of resveratrol on oral squamous cell carcinoma (OSCC) cells in vitro", J Cancer Res Clin Oncol, 140, pp.371~374 (2014)[DOI]
- Zhang Q, "Resveratrol inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1alpha and VEGF expression in human tongue squamous cell carcinoma and hepatoma cells", Mol Cancer Ther, 4, pp.1465~1474 (2005)[DOI]