The Effects of Deoxyelephantopin on the Akt/mTOR/P70S6K Signaling Pathway in MCF-7 Breast Carcinoma Cells In Vitro

Fazil, Wan Failiza Wan Mohamad; Amanah, Azimah; Abduraman, Muhammad Asyraf; Sulaiman, Shaida Fariza; Wahab, Habibah Abdul; Tan, Mei Lan

doi:10.1177/0976500X221114003

Research ArticleArchivesVol. 13 | Issue 2 | 2022 | pp. 148–159Open Access

The Effects of Deoxyelephantopin on the Akt/mTOR/P70S6K Signaling Pathway in MCF-7 Breast Carcinoma Cells In Vitro

¹,
¹,
²,
³,
³,
^1,2,3^*

¹Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), National Institutes of Biotechnology Malaysia (NIBM), Pulau Pinang, Malaysia.
²Advanced Medical and Dental Institute, Universiti Sains Malaysia, SAINS@BERTAM, Kepala Batas, Pulau Pinang, Malaysia.
³Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Pulau Pinang, Malaysia.

Correspondence: Mei Lan Tan
Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), National Institutes of Biotechnology Malaysia (NIBM), Pulau Pinang, Malaysia.; Advanced Medical and Dental Institute, Universiti Sains Malaysia, SAINS@BERTAM, Kepala Batas, Pulau Pinang, Malaysia.; Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Pulau Pinang, Malaysia.
Email: tanml@usm.my

Published: Jan 1, 2022, Received: Apr 29, 2022, Accepted: Jun 28, 2022

DOI: https://doi.org/10.1177/0976500X221114003
Article URL: https://www.jpharmacol.com/article/j-pharmacol-pharmacother-13-2-148
PDF URL: https://www.jpharmacol.com/article/j-pharmacol-pharmacother-13-2-148.pdf

Abstract

Objective: To determine the effects of deoxyelephantopin on mTOR and its related target molecules (Akt/mTOR/P70S6K) in the ER-positive breast cancer cell line.

Materials and Methods: Primary in silico simulations were determined, and the effects of deoxyelephantopin on the phosphorylation of the Akt/mTOR/P70S6K molecules were evaluated using AlphaScreen-based assays and western blot analysis, respectively.

Results: Based on the estimated FEB and Ki values, deoxyelephantopin appeared to have a stronger affinity toward P70S6K as compared with Akt and mTOR. Both deoxyelephantopin and control inhibitors were observed to form hydrogen bonds with the same key residue, Leu175 of the P70S6K molecule. Deoxyelephantopin downregulated the p-P70S6K protein expression significantly from 18 µM (p < 0.05) and onward. Based on the AlphaScreen assay, deoxyelephantopin produced a concentration-dependent inhibition on the phosphorylation of P70S6K with an IC50 value of 7.13 µM.

Conclusion: Deoxyelephantopin induced cell death in MCF-7 cells possibly via DNA fragmentation, inhibition of the phosphorylation of P70SK6, and downregulation of the relative p-p70S6K protein expression levels.

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