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 (LC50 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 RT2 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.

An insight into the anticancer mechanism of Tribulus terrestris extracts on human breast cancer cells

“…The values are expressed as means ± SD where *p value < 0.05 was considered when compared with control using one-sample t test extracts of TT indicating the probable triggering of extrinsic apoptotic pathway. Caspase-8 causes the activation of proenzyme caspase-3 to its active form by cleaving it into subunits and their dimerization (Basaiyye et al 2017). Caspase-3 is essential for the cleavage of DNA in cancer cells (Cucina et al 2009).…”

“…Natural compounds have been widely tested for their anticancer properties due to minimum side effects. Alkaloids, terpenoids, flavonoids, saponins, tannins, phenolics, etc., are some of naturally occurring active principals found in nature (Basaiyye et al 2017). Tribulus terrestris L. (TT) (Zygophyllaceae) is an annual herb that has been used in the traditional medicine all over the world (Graham et al 2000;Angelova et al 2013).…”

Cardiac protection induced by urocortin-2 enables the regulation of apoptosis and fibrosis after ischemia and reperfusion involving miR-29a modulation

“…The selection of these genes was based on their fold change rates as well as their implication in I/R-related processes, as published elsewhere. 20 , 21 , 22 Namely, we investigated the expression of Apoptosis Inducing Factor mitochondria associated 1 ( Aifm1 ), Apoptosis Protease-Activating Factor-1 ( Apaf1 ), B-Cell Lymphoma 2 ( Bcl-2 ), Cytochrome c ( Cycs ), Heme Oxygenase 1 ( Hmox-1 ), and Mitogen-Activated Protein Kinase 8 ( Mapk-8 ). Figures 6 A and 6B show that the expression of Apaf-1 and Hmox-1 increased significantly in I/R, as compared with controls.…”

Therapeutic natural compounds Enzastaurin and Palbociclib inhibits MASTL kinase activity preventing breast cancer cell proliferation

“…After 24 hrs of incubation, complete media was removed and cells were washed with 1X PBS. 20µl MTT (5 mg/ml) was added and further, incubated for 2hrs [19]. MTT was aspirated and formazan produced was dissolved in 100µl of 0.1% DMSO.…”