Chenopodium ambrosioides Linn. induces mitochondrial-dependent cell death via activation of mPT pore opening, caspases and apoptotic machinery.

Abstract

Objectives: Mitochondrion is an organelle involved in cellular energy generation and cell death. The mitochondrial permeability transition (mPT) pore plays a crucial role in the execution of mitochondrial-dependent cell death. Several medicinal plants evoke their therapeutic potential against tumor and cancer by instigating mitochondrial-dependent cell death. This research consequently explored the effect of chloroform fraction of Chenopodium ambrosioides (CFCA) on mitochondrial-dependent cell death via mPT pore.

Methodology: Rats were equally assigned into four groups; A (control), B (50), C (100) and D (200) mg/kg CFCA. Mitochondria were isolated by differential centrifugation. The mPT pore opening, mitochondrial ATPase (mATPase) activity and mitochondrial-lipid peroxidation (mLPO) were assessed spectrophotometrically. Caspases 9 and 3 levels, hepatic DNA fragmentation, histology and immunohistochemical analysis of Bax, Cytochrome c, P53 and anti-apoptotic Bcl-2 proteins were determined. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of CFCA was carried out.

Results: The CFCA dose-dependently induced mPT pore opening, enhanced mATPase activity, reduced malondialdehyde generation, increased Caspases 9 and 3 levels and effected hepatic DNA fragmentation. The histological assessment showed mild to moderate steatosis and infiltration of the hepatocytes. The CFCA upregulated the expression of Bax, Cytochrome c and P53 proteins while anti-apoptotic Bcl-2 protein was downregulated. The GC-MS analysis revealed the presence of certain pharmacologically reactive compounds including Tridecanoic acid, 12-methyl ester, Hexadecanoic acid methyl ester, 11-Octadecadienoic acid, methyl ester, Pyrido[2,3-d]pyrimidine and 6-Undecyl-5,6-dihydro-2H-pyran-2-one.

Conclusions: This study suggests the presence of phytochemicals in CFCA that could execute mitochondrial-mediated apoptosis via induction of mPT pore opening, caspases and apoptotic machinery.