Curcumin abrogates bile-induced NF-κB activity and DNA damage in vitro and suppresses NF-κB activity whilst promoting apoptosis in vivo, suggesting chemopreventative potential in Barrett's oesophagus.

INTRODUCTION: Curcumin has been suggested to possess anti-neoplastic properties. As oesophageal adenocarcinoma (OA) and Barrett's oesophagus (BO) represent a neoplastic series, we postulated that curcumin supplementation may slow neoplastic progression at this site. Our aim was to investigate the effects of curcumin in vitro and in vivo on markers of oesophageal cancer progression. METHODS: We investigated the in vitro ability of curcumin to prevent bile acid-induced DNA damage using micronucleus assay and nuclear factor-kappaB (NF-κB) activity in the oesophageal cell lines (OE33) using real-time PCR of the extracted RNA. We also analysed NF-κB p65 activation in curcumin-pre-treated OE33 cells exposed to deoxycholic acid (DCA) using ELISA. In another pilot study, BO patients took a daily 500 mg curcumin tablet for 7 days prior to their endoscopy. In biopsies collected from these patients (n=33, 16 curcumin, 17 control), we examined NF-κB-driven gene expression (interleukin (IL)-8, inhibitor- kappaB (I-κB)) using real-time PCR of the extracted RNA from the biopsy sample. The apoptotic frequency was assessed by counting the number of apoptotic bodies in the epithelial cells from the Barrett's tissue with and without curcumin. RESULTS: In vitro, curcumin (50 µM) significantly abrogated DNA damage and NF-κB activity induced by bile. Pretreating OE33 cells with curcumin (50 µM) completely abolished the ability of DCA (300 µM) to activate NF-κB. In vivo, IL-8 expression was non-significantly suppressed in the curcumin-supplemented patients compared to the squamous control tissue, whilst also showing a doubling in the apoptotic frequency compared to non-supplemented control patients. CONCLUSIONS: Curcumin abrogated bile-driven effects in vitro. The in vivo data also suggests that curcumin supplementation had beneficial effects (increased apoptosis, potentially reduced NF-κB activity) in the Barrett's tissues themselves, despite poor delivery of the curcumin to the oesophagus.

Marmoset evolution: the molecular evidence.

We report here the results of comparative immunological and electrophoretic studies of the serum proteins of the New World monkeys. Specifically, we find that the New World monkeys share a long period of common ancestry with the Catarrhini and that the divergence between these two groups occurred some 35-40 million years ago. The extant New World monkey lineages are then seen as sharing a long period of common ancestry subsequent to that divergence, with their radiation beginning in the early Miocene. We see seven distinct lineages stemming from this radiation: (1) Aotus, (2) Callicebus, (3) Cebus, (4) Saimiri, (5) Ateles-Lagothrix-Alouatta, (6) Pithecia-Cacajao and (7) Callimico-Callimico with Cebuella-Saguinus-Leontideus. Within those Ateles with Lagonthrix, and Callimico with Callithrix-Cebuella form further subgroups. The marmoset radiation appears to have begun some 7-10 million years ago.