Delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside mediate the redox-sensitive caspase 3-related pro-apoptotic effect of blackcurrant juice on leukaemia Jurkat cells

Abstract

Blackcurrant, a rich source of anthocyanins, has been reported to exhibit an antiproliferative effect on several types of solid tumour cancer cells, but its active molecules and the precise mechanism of their action remain unclear. The aim of the present study was to investigate the anticancer effect of blackcurrant-derived products (juice (BCJ), extract (BCE) and anthocyanins, namely cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside) in Jurkat cells and to characterize the underlying mechanism. Cell cycle and apoptosis were assessed by flow cytometry, the formation of reactive oxygen species (ROS) by dihydroethidine and protein expression by Western blotting. BCJ and BCE inhibited the proliferation and induced G2/M phase cell cycle arrest and apoptosis in Jurkat cells associated with an increased expression of p73 and caspase 3, dephosphorylation of Akt and Bad, and down-regulation of UHRF1 and Bcl-2. A pro-apoptotic response was also observed in response to two major blackcurrant anthocyanins, delphinidin-3-O-rutinoside and delphinidin-3-O-glucoside. The BCJ- and BCE-induced activation of caspase 3 was markedly inhibited by pretreatment with N-acetylcysteine. BCE and the two active anthocyanins induced the formation of reactive oxygen species. BCJ and its major anthocyanins induced a redox-sensitive caspase 3-dependent apoptosis in Jurkat cells, involving a dysregulation of the Akt/Bad/Bcl-2 pathway.

Keywords

• Blackcurrant
• Berry
• Anthocyanin
• Leukaemia
• Apoptosis
• p73