Modulation of Cytochrome C Release and Opening of Mitochondrial Permeability Transition Pore by Calliandra portoricensis (Benth) Root Bark Methanol Extract

Abstract

Aim: Evasion of apoptosis, a form of programmed cell death, is a common feature of most cancer cells. This study evaluated the modulatory effects of different fractions of crude methanol extract of the root bark of Calliandra portoricensis, a medicinal plant used in the traditional treatment of prostate tumour on cytochrome C release via opening of the mitochondrial Permeability Transition (mPT) pore in rat liver. Methodology: Opening of the pore, mitochondrial ATPase activity, cytochrome C release and extent of mitochondrial lipid peroxidation were assessed and monitored spectrophotometrically in vitro. Results: In the presence and absence of calcium, Vacuum Liquid Chromatography (VLC) Ethylacetate fraction (EFCP) had no effect at all concentrations tested. Varying concentrations (10-120 µg/mL) of VLC methanol fraction (MFCP) significantly induced pore opening in the absence of calcium by 2.7,3.9,9.7, 11.2, 12.5, 14.5 and 15.1 folds while spermine reversed this inductive effect.  In the presence of calcium, the pore was slightly further opened by MFCP. Furthermore, these fractions enhanced mitochondrial ATPase activity and diminished the extent of Fe2+-induced lipid peroxidation in a concentration-dependent manner with significant effect in MFCP. Similarly, cytochrome C release in MFCP was significant when compared to other fractions.   Conclusion: Taken together, these results suggest that bioactive agents that possess the potential of interfering with mitochondrial bioenergetics and inducing opening of the pore are present in the most potent methanol fraction of C. portoricensis, this would find use in disease conditions where apoptosis needs to be upregulated.