Modulation of the apoptotic effects of terpenes by acting on the mitochondrial Enzymatic system in hepatic normal and Cancer cells.

Abstract

Ferula vesceritensis roots are potential sources of natural antioxidant and prooxidant esquiterpenecoumarinsthat could potentially have antiproliferative, cytotoxic effects against many types of cancers including liver cancer which is the principle cause of death worldwide. The aim of this work is to investigate the biological activity of sesquiterpenecoumarins, ferulenol,coladin and lepiferin obtained from the Ferula roots crude methanol extract. These bioactive compounds whose structures determined by extension NMR analysis are explored in vivo and in vitro studies by following the prooxidant effects, tested on experimental liver cancer induced by Benzo(a)pyrane,and cytotoxic effects on B16F1 melanoma and FAO cell lines. The impact of these bioactive compounds over the mitochondrial function has also been evaluated in liver mitochondria. Ferulenol, coladin and lapiferin have increased the oxidative stress by variably decreasing the enzymatic and non enzymatic antioxidants (SOD CAT, GST) and increasing the lipid peroxidation as well as diminishing the mitochondrial dehydrogenases activities tested on Bl6F1 melanoma and FAO cells with MTT and WST-1 assay after 24 and 48 hrs throughout an apoptotic pathway.At the level of mitochondria, those bioactive substances have caused mitochondrial swelling and a variable diminution in the mitochondrial superoxide anion O-2productionin isolated mitochondrial liver in a dose dependant manner. The prooxidant, cytotoxic and/or chemopreventiveeffects of Ferulavesceritensis roots sesquiterpenecoumarins have permitted us to suggest the possible potential exploration of those bioactive compounds for combating and/or preventing many diseases such as liver cancer.