Pseurotin A Halts Hepatocellular Carcinoma Oncogenic Potential Through Tuning miR-30a and let-7i Tumor Suppressor miRNAs

Document Type : Original Article

Authors

1 Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo, Egypt

2 Department of Pharmacognosy ,Faculty of Pharmacy ,Cairo University ,Cairo

3 National research center, Cairo Microbial Chemistry department, National Research Centre, 33 El-Buhouth Street,

4 Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted By Global Academic Foundation, New Administrative Capital, Cairo, Egypt

Abstract

Hepatocellular carcinoma (HCC) is a global health challenge with a predicted high mortality rate in the future. Thus, discovering novel natural metabolites trimming the progression of HCC is an urgent necessity. In this study, we aimed to evaluate the effect of cytotoxic alkaloids isolated from endophytic fungus Aspergillus fumigatus, extracted from Albizia lucidior leaves (Fabaceae), against Huh7 cells and to further reveal their possible mechanisms on TP53 and c-Myc and their downstream tumor suppressor microRNAs (miRNAs). Pseurotin A and chaetominine revealed a concentration and time-dependent inhibition in cellular viability of Huh7 cells as well as significant repression in the proliferation and clonogenic capacities of Huh7 cells, compared to vehicle control. Pseurotin A exhibited more potent effects in halting Huh7 tumorigenic activity than chaetominine. Restoration of TP53, c-Myc, and their downstream tumor suppressor miRNAs; miR-30a, let-7i was achieved by pseurotin A only. Therefore, this study highlights a novel role of alkaloidal compounds from A. fumigatus in controlling the progression of HCC.

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Volume 65, Issue 13 - Serial Number 13
Special Issue: Chemistry and Global Challenges
December 2022
  • Receive Date: 28 May 2022
  • Revise Date: 25 June 2022
  • Accept Date: 26 June 2022
  • First Publish Date: 26 June 2022