Resveratrol attenuates matrix metalloproteinase-9 and -2-regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways

Gweon,Eun Jeong; Kim,Song-Ja

doi:10.3892/or.2014.3192

Resveratrol attenuates matrix metalloproteinase-9 and -2-regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways

Authors:
- Eun Jeong Gweon
- Song-Ja Kim
View Affiliations

Affiliations: Department of Biological Sciences, College of Natural Sciences, Kongju National University, Chungnam 314-701, Republic of Korea
Published online on: May 16, 2014 https://doi.org/10.3892/or.2014.3192
Pages: 71-78

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Resveratrol has been shown to possess anticancer, anti-aging, and anti-inflammatory properties. Matrix metalloproteinases (MMPs) appear to be responsible for much of the extracellular matrix (ECM) degradation observed in the progression of cancer, aging and inflammation. We found that resveratrol significantly inhibited MMP-2 and MMP-9, and induced the expression of type II collagen and sex-determining region Y-box (SOX)-9 and the production of sulfated proteoglycans in HTB94 chondrosarcoma cells. Moreover, inhibition of MMPs with an MMP inhibitor further enhanced the effects of resveratrol. Phosphorylation of p38 was increased and phosphorylation of c-Jun N-terminal kinase (JNK) was inhibited by resveratrol. Treatment with SB203580, a p38 kinase inhibitor, enhanced the suppression of MMP-2 and MMP-9 by resveratrol and inhibited resveratrol-induced stimulation of type II collagen and SOX-9 expression and production of sulfated proteoglycans. Treatment with SP600125, a JNK inhibitor, attenuated the effects of resveratrol on MMP-2 and MMP-9, and accelerated resveratrol-induced effects on type II collagen, SOX-9 and sulfated proteoglycan production. Our results suggest that resveratrol inhibits MMP-induced differentiation via the p38 kinase and JNK pathways in HTB94 chondrosarcoma cells.

View Figures

View References

1	Zyada MM and Shamaa AA: Is collagenase-3 (MMP-13) expression in chondrosarcoma of the jaws a true marker for tumor aggressiveness? Diagn Pathol. 3:262008. View Article : Google Scholar : PubMed/NCBI
2	Tang CH and Tsai CC: CCL2 increases MMP-9 expression and cell motility in human chondrosarcoma cells via the Ras/Raf/MEK/ERK/NF-κB signaling pathway. Biochem Pharmacol. 83:335–344. 2012.PubMed/NCBI
3	Power PF, Mak IW, Singh S, Popovic S, Gladdy R and Ghert M: ETV5 as a regulator of matrix metalloproteinase 2 in human chondrosarcoma. J Orthop Res. 31:493–501. 2013. View Article : Google Scholar : PubMed/NCBI
4	Lu YC, Jayakumar T, Duann YF, et al: Chondroprotective role of sesamol by inhibiting MMPs expression via retaining NF-κB signaling in activated SW1353 cells. J Agric Food Chem. 59:4969–4978. 2011.PubMed/NCBI
5	Im HJ, Li X, Chen D, et al: Biological effects of the plant-derived polyphenol resveratrol in human articular cartilage and chondrosarcoma cells. J Cell Physiol. 227:3488–3497. 2012. View Article : Google Scholar : PubMed/NCBI
6	Hidalgo M and Eckhardt SG: Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst. 93:178–193. 2001. View Article : Google Scholar : PubMed/NCBI
7	Abeles AM and Pillinger MH: The role of the synovial fibroblast in rheumatoid arthritis: cartilage destruction and the regulation of matrix metalloproteinases. Bull NYU Hosp Jt Dis. 64:20–24. 2006.PubMed/NCBI
8	Tchetverikov I, Lohmander LS, Verzijl N, et al: MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann Rheum Dis. 64:694–698. 2005. View Article : Google Scholar
9	Brisdelli F, D’Andrea G and Bozzi A: Resveratrol: a natural polyphenol with multiple chemopreventive properties. Curr Drug Metab. 10:530–546. 2009. View Article : Google Scholar : PubMed/NCBI
10	Lee SJ and Kim MM: Resveratrol with antioxidant activity inhibits matrix metalloproteinase via modulation of SIRT1 in human fibrosarcoma cells. Life Sci. 88:465–472. 2009.
11	Liu FC, Hung LF, Wu WL, et al: Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes. Arthritis Res Ther. 12:R1672010. View Article : Google Scholar : PubMed/NCBI
12	Lee HS, Ha AW and Kim WK: Effect of resveratrol on the metastasis of 4T1 mouse breast cancer cells in vitro and in vivo. Nutr Res Pract. 6:294–300. 2012. View Article : Google Scholar : PubMed/NCBI
13	Liu PL, Tsai JR, Charles AL, et al: Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-κB pathway and subsequently downregulating expression of matrix metalloproteinases. Mol Nutr Food Res. 54(Suppl 2): S196–S204. 2010.PubMed/NCBI
14	Dhillon AS, Hagan S, Rath O and Kolch W: MAP kinase signalling pathways in cancer. Oncogene. 26:3279–3290. 2007. View Article : Google Scholar : PubMed/NCBI
15	Kim SJ, Ju JW, Oh CD, et al: ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status. J Biol Chem. 277:1332–1339. 2002. View Article : Google Scholar : PubMed/NCBI
16	Cohen M, Meisser A, Haenggeli L and Bischof P: Involvement of MAPK pathway in TNF-α-induced MMP-9 expression in human trophoblastic cells. Mol Hum Reprod. 12:225–232. 2006.
17	Kajanne R, Miettinen P, Mehlem A, et al: EGF-R regulates MMP function in fibroblasts through MAPK and AP-1 pathways. J Cell Physiol. 212:489–497. 2007. View Article : Google Scholar : PubMed/NCBI
18	Kim ES, Sohn YW and Moon A: TGF-β-induced transcriptional activation of MMP-2 is mediated by activating transcription factor (ATF) 2 in human breast epithelial cells. Cancer Lett. 252:147–156. 2007.
19	Azios NG and Dharmawardhane SF: Resveratrol and estradiol exert disparate effects on cell migration, cell surface actin structures, and focal adhesion assembly in MDA-MB-231 human breast cancer cells. Neoplasia. 7:128–140. 2005. View Article : Google Scholar
20	Park JS, Kim KM, Kim MH, et al: Resveratrol inhibits tumor cell adhesion to endothelial cells by blocking ICAM-1 expression. Anticancer Res. 29:355–362. 2009.PubMed/NCBI
21	Hwang JT, Kim S, Choi I and Choi SY: Resveratrol analog 4-[2-(3,5-dimethoxyphenyl)vinyl]pyridine reduces differentiation of the 3T3-L1 adipocyte. Pharm Biol. 51:96–99. 2013.
22	Hou CH, Chiang YC, Fong YC and Tang CH: WISP-1 increases MMP-2 expression and cell motility in human chondrosarcoma cells. Biochem Pharmacol. 81:1286–1295. 2011. View Article : Google Scholar : PubMed/NCBI
23	Tang CH, Chen CF, Chen WM and Fong YC: IL-6 increases MMP-13 expression and motility in human chondrosarcoma cells. J Biol Chem. 286:11056–11066. 2011. View Article : Google Scholar : PubMed/NCBI
24	Shinomura T, Ito K, Hook M and Kimura JH: A newly identified enhancer element responsible for type II collagen gene expression. J Biochem. 152:565–575. 2012. View Article : Google Scholar : PubMed/NCBI
25	Jawad MU, Garamszegi N, Garamszegi SP, et al: Matrix metalloproteinase 1: role in sarcoma biology. PLoS One. 5:e142502010. View Article : Google Scholar : PubMed/NCBI
26	Wu MH, Lo JF, Kuo CH, et al: Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways. J Cell Physiol. 227:3016–3026. 2012. View Article : Google Scholar : PubMed/NCBI
27	Lim H and Kim HP: Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways. Arch Pharm Res. 34:109–117. 2011.
28	Park HY, Lim H, Kim HP and Kwon YS: Downregulation of matrix metalloproteinase-13 by the root extract of Cyathula officinalis Kuan and its constituents in IL-1β-treated chondrocytes. Planta Med. 77:1528–1530. 2011. View Article : Google Scholar : PubMed/NCBI
29	Tzeng HE, Chen JC, Tsai CH, et al: CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma through integrin-dependent pathway. J Cell Physiol. 226:3181–3189. 2011. View Article : Google Scholar : PubMed/NCBI