Apoptosis of Bel-7402 human hepatoma cells induced by a ruthenium(II) complex coordinated by cordycepin through the p53 pathway

Abstract

A ruthenium(II) complex coordinated by cordycepin, [Cor‑Ru(II)], was synthesized for investigation as a potential novel candidate for cancer therapy. The antitumor activity of Cor‑Ru(II) was investigated by MTT and flow cytometry (FCM) assays. The results showed that Cor‑Ru(II) significantly inhibited the proliferation of Bel‑7402 human hepatoma cells and delayed cell cycle progression. Subsequent experiments using FCM and western blot analysis indicated that Cor‑Ru(II) induced cell apoptosis via suppression of bcl‑2 expression and stimulation of p53 expression. Cor‑Ru(II) was shown to interfere with the synthesis of DNA. This was confirmed by the in vitro binding to DNA in the groove binding mode (Kb=4.22(±0.2)x10(5) M(‑1)). Thus, Cor‑Ru(II) appears to act as an effective antitumor agent in vitro.

Influence of nitric oxide signaling mechanisms in cancer

“…Therefore, the activity of p53 is essential in suppressing tumors by different routes, such as inducing apoptosis and DNA repair and participating in cell cycle arrest. [41][42][43][44][45] Recent studies have suggested the involvement of NO in the suppression of p53 by reactive nitrogen species, which are produced from the reaction of NO with superoxide anion and other free radicals and nitration of tyrosine residues by the action of peroxynitrite generated from NO. Thus, the tyrosine residues are "nitro" group acceptors and they become 3-nitrotyrosine; this event can alter the structure and function of p53, reducing its activity and contributing to cancer development.…”

“…Therefore, the activity of p53 is essential in suppressing tumors by different routes, such as inducing apoptosis and DNA repair and participating in cell cycle arrest. 41–45…”