Presentation: Resveratrol Induces the Apoptosis in Synovial Fibroblasts of Rheumatoid Arthritis (2007)

1780 Resveratrol Induces the Apoptosis in Synovial Fibroblasts of Rheumatoid Arthritis

PURPOSE: Resveratrol (trans-3,4’,5-trihydroxystilbene), a polyphenolic phytoalexin, is a very effective anti-oxidant that also exhibits strong anti-proliferative and anti-inflammatory properties. Although recent studies have provided support for the use of resveratrol in human cancer chemoprevention, in combination with either chemotherapeutic drugs or cytotoxic factors for a most efficient treatment of drug refractory tumor cells, the effect of resveratrol on the cellular death signaling in rheumatoid arthritis (RA) has never been assessed. This study was conducted to evaluate the anti-proliferative potential of resveratrol against primary human synovial fibroblasts of RA (SFRA) and its molecular mechanism of action.
METHODS: The effects of resveratrol on the apoptosis of cultured RASF were examined in vitro. Apoptosis was analyzed by flow cytometry after staining with propiduim iodide, western blot for caspase-3, 8, 9 and PARP. We examined mitochondrial membrane permeability (MMP) as measured by a Rhodamine 123 and the release of cytochrome c, and AIF (apoptosis inducing factor). Whether the effect of resveratrol on apoptosis depends on p53, we use wild type MEFs, p53-/-MEFs and PFTa (inhibitor of p53).
RESULTS: The decrease in survival of RASF was demonstrated to be associated with a time and concentration of resveratrol. Resveratrol activates the apoptotic cascade via the disruption of mitochondrial membrane potential and subsequent releases of cytochrome c and AIF form mitochondria to cytosol. Interestingly, the p53-/-MEFs also showed the similar rate of apoptosis and loss of MMP, compared to that of wild type MEFs, suggesting that resveratrol induces an apoptotic cell death in a p53-independent manner. Furthermore, our data showed that resveratrol-treatment resulted in significant activation of caspase-8.
CONCLUSIONS: Our data showed that resveratrol causes mitochondrial membrane disruption to result an activation of caspase-8 and to lead an active apoptosome complex. These findings suggest that the natural product resveratrol has potential as novel therapeutic agents for rheumatoid arthritis.
Keywords : resveratrol, rheumatoid arthritis, apoptosis, synovial fibroblast

 J. Song, None; J. Hwang, None; H. Byun, None; Y. Lee, None; G. Hur, None; S. Kang, None.