Molecular mechanism of apoptosis induction in Jurkat E6-1 cells by Tribulus terrestris alkaloids extract
| Autor: | Kannan Krishnamurthi, Amit Bafana, Shriniwas S. Basaiyye, Saravanadevi Sivanesan, Pravin K. Naoghare, Sanjeev Kanojiya, Patrizio Arrigo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Tribulus biology Chemistry Alkaloid lcsh:R lcsh:Medicine biology.organism_classification Jurkat cells 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Complementary and alternative medicine Biochemistry Apoptosis 030220 oncology & carcinogenesis biology.protein DNA fragmentation Tumor necrosis factor receptor 1 FADD Cytotoxicity |
| Zdroj: | Journal of Traditional and Complementary Medicine, Vol 8, Iss 3, Pp 410-419 (2018) |
| ISSN: | 2225-4110 |
| Popis: | 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. Keywords: Tribulus terristris L., Cytotoxicity, Apoptosis, N-feruloyltyramine, In silico |
| Databáze: | OpenAIRE |
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