Antitumoral actions of Vismia baccifera on human hepatocellular carcinoma HepG2

Abstract

Nowadays there is an increasing interest in finding bioactive compounds which can be used as chemopreventive agents against cancer. In this work, we have studied the antitumoral actions of aqueous extracts from leaves of the Colombian Amazonian Vismia baccifera plant on the human hepatocellular carcinoma HepG2 cell line. Our results showed that V. baccifera induced a cytotoxic response to HepG2, increasing the levels of mitochondrial O2- and intracellular ROS (particularly hydrogen peroxide), inducing depletion of GSH, cell cycle arrest at G2/M phase, endoplasmic reticulum stress, autophagy and apoptosis. Interestingly, the cytotoxic actions exerted by V. baccifera are exclusive of cancer cells. Hydrogen peroxide, whose intracellular accumulation was early induced by the extract, mediated the cytotoxic response. V. baccifera promoted deregulation of antioxidant enzymes, this effect being secondary to the accumulation of ROS. The intracellular GSH depletion was not the cause, but the consequence of V. baccifera-induced toxicity. The plant extract also affected HepG2 signaling by activating and inhibiting specific pathways. Moreover, we validated the experimental approach we have used to study the toxic response under conditions of 21% atmospheric pO2, ruling out any possible superimposed oxidative stress derived from the culture conditions. Our results highlight the importance of analyzing in depth the actions of this plant to generate knowledge that can lay the bases for coadjuvant or anti-cancer therapy.