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

Abstract

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.

Efficacy of resveratrol to supplement oral nifedipine treatment in pregnancy-induced preeclampsia

“…Besides sFlt-1, matrix metalloproteinase (MMP)-2 and MMP-9 were also reported to be involved in the pathology of PE, both as predictive biomarkers and as drug targets (30, 31, 32, 33). Given the great body of studies reporting the function of RESV in regulating levels and activities of both MMP-2 and MMP-9 (34, 35, 36, 37), these two MMPs are also likely to be the mediating factor of RESV in relieving hypertension of PE patients. Further studies are currently underway to evaluate the above potential mechanisms, particularly a larger scale multicenter trial is needed.…”

Sphingosine‐1‐phosphate suppresses chondrosarcoma metastasis by upregulation of tissue inhibitor of metalloproteinase 3 through suppressing miR‐101 expression

“…Thus, understanding or regulation of the metastatic processes on chondrosarcoma is a strategy for the treatment of this disease. Increasing evidence indicates that upregulation of MMPs is required for metastasis in several cancers, including chondrosarcoma, and is also responsible for their poor prognosis (Gweon and Kim, ). MMPs therefore represent the potential target for preventing cancer metastasis, especially targeting for MMP‐2.…”

Resveratrol improves delayed r-tPA treatment outcome by reducing MMPs

“…Moreover, resveratrol alleviated the BBB dysfunction by regulating the MMP‐9/TIMP‐1 balance after cerebral ischemia reperfusion in rats . In HTB94 chondrosarcoma cells, resveratrol significantly inhibited MMP‐2 and MMP‐9 through the p38 kinase and JNK pathways . As mentioned above, delayed r‐tPA administration results in up‐regulation of MMPs that in turn disrupts BBB; therefore, in this context, the use of resveratrol could attenuate the MMP up‐regulation caused by delayed r‐tPA.…”