Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

In Vitro and In Silico Analysis of the Anti-cancer Effects of Eurycomanone and Eurycomalactone from Eurycoma longifolia.

Version 1 : Received: 16 May 2023 / Approved: 17 May 2023 / Online: 17 May 2023 (03:23:26 CEST)
Version 2 : Received: 22 May 2023 / Approved: 22 May 2023 / Online: 22 May 2023 (11:02:09 CEST)

A peer-reviewed article of this Preprint also exists.

Yunos, N.M.; Wahab, H.A.; Al-Thiabat, M.G.; Sallehudin, N.J.; Jauri, M.H. In Vitro and In Silico Analysis of the Anticancer Effects of Eurycomanone and Eurycomalactone from Eurycoma longifolia. Plants 2023, 12, 2827. Yunos, N.M.; Wahab, H.A.; Al-Thiabat, M.G.; Sallehudin, N.J.; Jauri, M.H. In Vitro and In Silico Analysis of the Anticancer Effects of Eurycomanone and Eurycomalactone from Eurycoma longifolia. Plants 2023, 12, 2827.

Abstract

Eurycomanone and eurycomalactone are known quassinoids present in the roots and stems of Eurycoma longifolia. These compounds had been reported to have cytotoxic effects, however, their mechanism of action in a few cancer cell lines have yet to be elucidated. This study was aimed to investigate the anti-cancer effects and mechanisms of action of eurycomanone and eurycomalactone in cervical (HeLa), colorectal (HT29) and ovarian (A2780) cancer cell lines via Sulforhodamine B assay. Their mechanism of cell death was evaluated based on Hoechst 33342 assay and in silico molecular docking toward DHFR and TNF-α as putative protein targets. Eurycomanone and eurycomalactone exhibited in vitro anti-cancer effects manifesting IC50 values of 4.58 ± 0.090 µM and 1.60 ± 0.12 µM (HeLa), 1.22 ± 0.11 µM and 2.21 ± 0.049 µM (HT-29), and 1.37 ± 0.13 µM and 2.46 ± 0.081 µM (A2780) respectively. They induced apoptotic cancer cell death in dose- and time-dependent manners. Both eurycomanone and eurycomalactone were also predicted to have good inhibitory potential as demonstrated by the docking into TNF-α with binding affinity of -8.83 and -7.51 kcal/mol, respectively, as well as into DHFR with binding affinity results of -8.05 and -8.87 kcal/mol, respectively. These results support the evidence of eurycomanone and eurycomalactone as anti-cancer agents via apoptotic cell death mechanism that could be associated with TNF-α and DHFR inhibition as among possible protein targets.

Keywords

Eurycoma longifolia; quassinoids; cancer cell lines; apoptosis; TNF-α; DHFR; molecular docking; ADMET.

Subject

Medicine and Pharmacology, Medicine and Pharmacology

Comments (1)

Comment 1
Received: 22 May 2023
Commenter: Nurhanan Yunos
Commenter's Conflict of Interests: Author
Comment: 1) Title: In vitro and in silico analysis of the anti-cancer effects of eurycomanone and eurycomalactone from Eurycoma longifolia.
(Inserted the word 'of' in between 'anti-cancer effects' and 'eurycomanone'
2) Line 64 being corrected as "..have anti-malaria [14], anti-inflammatory [15] and anti-viral [16] properties."
3) Line 99-101 being corrected as: 
In our previous proteomic analysis, we found that TNF-α was involved in apoptosis when treated with 9-methoxycanthin-6-one, another compound that was also isolated from E. longifolia [32]. 
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