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When cells were treated first with doxycycline for 24?h and thereafter with zapotin for another 24?h (Dox 24?h?+?Zap 24?h), a significant (P?Ulixertinib manufacturer of c-Fos protein expression was demonstrated (Fig.?8A). The transcription factor NF-��B is involved in inhibition of apoptosis. Upon activation, an I��B kinase/NF-��B complex is split and NF��B is translocated to the nucleus to activate a series of genes. In an alternative pathway it is activated by phosphorylation. As shown in Fig.?8B, NF-��B levels were not altered or translocated to the nucleus significantly under zapotin treatment. However, the phosphorylated form of NF-��B was reduced after each of the zapotin treatments, indicating less inhibition of apoptosis. Plants represent a rich source of pharmacologically active compounds. Flavones, representing the flavonoid family, have potent anticancer properties. They have also been shown to exert chemopreventive effects (Cuendet et al., 2008, Gupta et al., 2002, Lepley et al., 2006, Lim et al., 2007?and?Murakami et al., 2000) by modulating proliferation and differentiation and inducing apoptosis in colon (Pan et al., 2002), breast (Ullmannova and Popescu, 2007) and prostate cancer cells (Gupta et al., 2002?and?Lepley et al., 2006). An increased number of methoxyl groups in the basic skeleton of the aglycone of flavones, especially in the A ring (Fig.?1), results in selleck an increased antiproliferative activity (Li et al., 2007?and?Walle, 2007). Moreover, inhibition of proliferation by flavones was observed selectively in cancer cells (Walle, 2007). A high antiproliferative potential of the polymethoxyflavones tangeretin and nobiletin is well documented in various types of cancers (Li et al., 2007?and?Morley et al., 2007). Cytotoxic activity of the tetramethoxyflavone zapotin, isolated from Casimiroa edulis was demonstrated in T24 and HepG2 cells ( Maiti et al., 2007). The present study showed that the IC50 value for inhibition of proliferation was lower in cells overexpressing constitutively active PKC�� than in HeLaWT cells (7.6 vs. 17.9?��M). PKC�� is known to play a crucial role in neoplastic transformation ( Hofmann, 2004?and?Jobbagy et al., 1999). Overexpression of PKC�� has been observed in cancer of the prostate, CASK lung, breast, liver and thyroid gland. PKC�� has been reported to be associated with tumor promotion along the Ras/Raf/MAPK phosphorylation cascade ( Bae et al., 2007, Basu and Sivaprasad, 2007?and?England et al., 2001). It was reported that in MCF7 breast cancer cells, overexpression of PKC�� mediates an antiapoptotic effect partly by preventing activation and translocation of Bax to the mitochondria ( Lu et al., 2007). PKC�� downregulation may thus represent one anticancer strategy. As shown in Fig.