Grape Seed Proanthocyanidins Induce Apoptosis through p53, Bax, and Caspase 3 Pathways

Grape seed proanthocyanidins (GSP) have been shown to inhibit skin chemical carcinogenesis and photocarcinogenesis in mice. The mechanisms responsible for the anticarcinogenic effects of GSP are not clearly understood. Here, we report that treatment of JB6 C141 cells (a well-developed cell culture model for studying tumor promotion in keratinocytes) and p53(+/+) fibroblasts with GSP resulted in a dose-dependent induction of apoptosis. GSP-induced (20–80 g/ml) apoptosis was observed by using immunofluorescence (27–90% apoptosis) and flow cytometry (18–87% apoptosis). The induction of apoptosis by GSP was p53-dependent because it occurred mainly in cells expressing wild-type p53 (p53(+/+); 15–80%) to a much greater extent than in p53-deficient cells (p53(-/-); 6–20%). GSP-induced apoptosis in JB6 C141 cells was associated with increased expression of the tumor-suppressor protein, p53, and its phosphorylation at Ser(15). The antiapoptotic proteins, Bcl-2 and Bcl-xl, were downregulated by GSP, whereas the expression of the pro-apoptotic protein, Bax, and the levels of cytochrome c release, Apaf-1, caspase-9, and cleaved caspase 3 (p19 and p17) were markedly increased in JB6 C141 cells. The downregulation of Bcl-2 and upregulation of Bax were also observed in wild-type p53 (p53(+/+)) fibroblasts but was not observed in their p53-deficient counterparts. These data clearly demonstrate that GSP-induced apoptosis is p53-dependent and mediated through the Bcl-2, Bax, and caspase 3 pathways

Detection of a quasi-periodic oscillation in the optical light curve of the remarkable blazar AO 0235+164

We present a long term optical $R$ band light curve analysis of the gravitationally lensed blazar AO 0235+164 in the time span 1982 - 2019. Several methods of analysis lead to the result that there is a periodicity of ~8.13 years present in these data. In addition, each of these five major flares are apparently double-peaked, with the secondary peak following the primary one by ~2 years. Along with the well known system, OJ 287, our finding constitutes one of the most secure cases of long term quasi-periodic optical behaviour in a blazar ever found. A binary supermassive black hole system appears to provide a good explanation for these results.Comment: 7 pages, 3 figures, 1 table, Accepted for publication in MNRA