Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC δ signal transduction

Woo, Ju Hyung; Lim, Jun Hee; Kim, Young Ho; Suh, Seong Il; Min, Do Sik; Chang, Jen-Yuan; Lee, Young Han; Park, Jong Wook; Kwon, Taeg Kyu

doi:10.1038/sj.onc.1207307

Cited by 220 publications

(172 citation statements)

References 30 publications

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“…Wild type of MMP-9 promoter and NF-kB-mutated MMP-9 promoter were kindly provided by Dr Taeg Kyu Kwon (Keimyung University, Daegu, South Korea) and were described previously (Woo et al, 2004). uPA promoter in luciferase reporter gene plasmid pGL2 basic was kindly provided by Dr Gordon B.…”

Section: Plasmids and Site-direct Mutagenesismentioning

confidence: 99%

The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion

et al. 2012

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Section: Plasmids and Site-direct Mutagenesismentioning

confidence: 99%

The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion

et al. 2012

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“…These results are in agreement with a previous study showing that RES inhibited MMP-9 mRNA expression by a mechanism involving NF-kB and AP-1. 72 Thus, the inhibitory effect of RES on NF-kB decreased the activity of the extracellular protease MMP-9, which contributes to tumor cell migration. The mechanism proposed for RES-induced apoptosis in MCF-7 cells is summarized in Figure 10.…”

Section: Discussionmentioning

confidence: 98%

Resveratrol‐induced apoptosis in MCF‐7 human breast cancer cells involves a caspase‐independent mechanism with downregulation of Bcl‐2 and NF‐κB

Pozo‐Guisado

Merino

Mulero‐Navarro

et al. 2005

Intl Journal of Cancer

209

143

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Resveratrol (RES), a chemopreventive molecule, inhibits the proliferation of tumor cells of different etiologies. We previously showed that RES alters the cell cycle and induces apoptosis in MCF-7 breast tumor cells by interfering with the estrogen receptor (ERa)-dependent phosphoinositide 3-kinase (PI3K) pathway. Here, we analyzed signaling downstream of PI3K, to understand the mechanisms of RES-induced apoptosis. Apoptotic death by RES in MCF-7 was mediated by Bcl-2 downregulation since overexpression of this protein abolished apoptosis. Decreased Bcl-2 levels were not related to cytochrome c release, activation of caspases 3/8 or poly(ADP-ribose) polymerase proteolysis. However, RES decreased mitochondrial membrane potential and increased reactive oxygen species and nitric oxide production. NF-kB, a regulator of Bcl-2 expression, and calpain protease activity, a regulator of NF-kB, were both inhibited by RES. The patterns for NFkB and calpain activities followed that of PI3K and were inhibited by LY294002. NF-kB inhibition coincided with diminished MMP-9 activity and cell migration. These data suggest that RES-induced apoptosis in MCF-7 could involve an oxidative, caspase-independent mechanism, whereby inhibition of PI3K signaling converges to Bcl-2 through NF-kB and calpain protease activity. Therefore, Bcl-2 and NF-kB could be considered potential targets for the chemopreventive activity of RES in estrogen-responsive tumor cells. ' 2005 Wiley-Liss, Inc.Key words: resveratrol; caspase; Bcl-2; NF-kB; apoptosis Among natural compounds with beneficial effects on human health, RES (3,4 0 ,5-trihydroxystilbene) has attracted considerable interest. This molecule, present at relevant concentrations in red wine, 1 has been associated with a lower incidence of cardiovascular disease. Different studies have also suggested a beneficial effect of RES in cancer since it inhibits proliferation and promotes death in tumor cell lines of different origins, 2-4 and, in vivo, suppresses the formation of skin 5 and mammary gland 6 tumors in rodent models of carcinogenesis.We, as well as other laboratories, have found that the ability of RES to inhibit cell viability and proliferation in the human breast cancer cell lines MCF-7 and MDA-MB-231 was unrelated to ERa status. 7,8 However, apoptotic cell death was present only in ERapositive MCF-7 and involved cell-specific regulation of the G 1 /S and G 2 /M transitions of the cell cycle. 2,8 RES properties are related to ERa since this compound has estrogenic or antiestrogenic activities depending on its concentration and the phenotype of the target cell. 9,10 ERa, in addition to its nuclear role as a transcription factor, is involved in regulating the PI3K pathway, which controls cell growth, proliferation and apoptosis. [11][12][13] In MCF-7 cells, RES induced a biphasic pattern of PI3K activity that increased at low concentrations and decreased at high concentrations. Activation of downstream PI3K effectors PKB/AKT and GSK-3 closely followed the pattern of PI3K activity. 14 The ...

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“…Moreover, pretreatment of chondrocytes with celecoxib, a selective COX-2 inhibitor that blocks PGE 2 synthesis, had effects similar to those of resveratrol on proteoglycan synthesis and MMP levels (39). Resveratrol-mediated down-regulation of MMP-9 via inhibition of JNK and protein kinase C activation has been reported in human cervical cancer cells following PMA activation (40); however, the role of PGE 2 in this process was not investigated.…”

Section: Discussionmentioning

confidence: 99%

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

Dave

Attur

Palmer

et al. 2008

Arthritis & Rheumatism

122

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Objective. To determine the effects of the antioxidant resveratrol on the functions of human chondrocytes in osteoarthritis (OA).Methods. Chondrocytes and cartilage explants were isolated from OA patients undergoing knee replacement surgery. Effects of resveratrol in the presence or absence of interleukin-1␤ (IL-1␤) stimulation were assessed by measurement of prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) synthesis, cyclooxygenase (COX) activity, matrix metalloproteinase (MMP) expression, and proteoglycan production. To explore the mechanisms of action of resveratrol, its effects on mitochondrial function and apoptosis were examined by assessing mitochondrial membrane potential, ATP levels, cytochrome c release, and annexin V staining.Results. Resveratrol inhibited both spontaneous and IL-1␤-induced PGE 2 production by >20% (P < 0.05) and by 80% (P < 0.001), respectively; similarly, LTB 4 production was reduced by >50% (P < 0.05). The production of PGE 2 was inhibited via a 70-90% suppression of COX-2 expression and enzyme activity (P < 0.05). Resveratrol also promoted anabolic effects in OA explant cultures, by elevating proteoglycan synthesis and decreasing production of MMPs 1, 3, and 13. Pretreatment of OA chondrocytes with resveratrol blocked mitochondrial membrane depolarization, loss of mitochondrial biomass, and IL-1␤-induced ATP depletion. Similarly, IL-1␤-mediated induction of the apoptotic markers cytochrome c and annexin V was also inhibited by resveratrol. Exogenous addition of PGE 2 abolished the protective effects of resveratrol on mitochondrial membrane integrity, ATP levels, expression of apoptotic markers, and DNA fragmentation.Conclusion. Resveratrol protects against IL-1␤-induced catabolic effects and prevents chondrocyte apoptosis via its inhibition of mitochondrial membrane depolarization and ATP depletion. These beneficial effects of resveratrol are due, in part, to its capacity to inhibit COX-2-derived PGE 2 synthesis. Resveratrol may therefore protect against oxidant injury and apoptosis, which are main features of progressive OA.

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Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC δ signal transduction

Cited by 220 publications

References 30 publications

The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion

The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion

Resveratrol‐induced apoptosis in MCF‐7 human breast cancer cells involves a caspase‐independent mechanism with downregulation of Bcl‐2 and NF‐κB

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

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