Molecular mechanism of apoptosis induction in Jurkat E6-1 cells by Tribulus terrestris alkaloids extract

Abstract The present study demonstrates apoptosis-inducing potential and mechanism of action of Tribulus terristris alkaloid extract in Jurkat E6-1 cancer cell line. Liquid Chromatography-Mass Spectrometry and High Resolution-Mass Spectrometry analysis identified the presence of four N -feruloyltyramine derivatives, namely trans- N -feruloyl-3-hydroxytyramine ( 1 ), trans- N -coumaroyltyramine ( 2 ), trans- N -feruloyltyramine ( 3 ) and trans- N -feruloyl-3-ethoxytyramine ( 4 ) in the alkaloid extract. Compounds 2 and 3 have not been yet reported in the alkaloid extract of T. terristris . In silico analysis revealed therapeutic potential of N -feruloyltyramine derivatives and strong binding efficiency to both chains of Tumor Necrosis Factor Receptor 1. Treatment of alkaloids extract to Jurkat E6-1 clone induced dose-dependent cytotoxicity (LC 50 140.4 μg mL −1 ). Jurkat cells treated with alkaloids extract at sub-lethal concentration showed DNA fragmentation, enhancement in caspase-3 activity and phosphatidylserine translocation (apoptosis indicator) compared to control cells. Gene expression analysis using Human Apoptosis RT 2 Profiler PCR Array analysis upon alkaloid treatment was found to significantly alter expression of critical genes such as TNFR1, FADD, AIFM, CASP8, TP53, DFFA and NFKB1 . These genes are predicted to mediate apoptotic cell death via both intrinsic and extrinsic apoptosis pathway. In summary, we report the identification of new N -feruloyltyramine derivatives from alkaloid extract of T . terristris fruit with probable anti-leukemic and pharmacological potential.