Involvement of autophagy in diosgenin‑induced megakaryocyte differentiation in human erythroleukemia cells

Diab,Dima; Pinon,Aline; Ouk,Catherine; Hage‑Sleiman,Rouba; Diab‑Assaf,Mona; Liagre,Bertrand; Leger,David Yannick

doi:10.3892/mmr.2021.12386

Involvement of autophagy in diosgenin‑induced megakaryocyte differentiation in human erythroleukemia cells

Authors:
- Dima Diab
- Aline Pinon
- Catherine Ouk
- Rouba Hage‑Sleiman
- Mona Diab‑Assaf
- Bertrand Liagre
- David Yannick Leger
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Affiliations: PEIRENE Laboratory EA 7500, Faculty of Pharmacy, University of Limoges, 87025 Limoges, France, BISCEm Flow Cytometry/Microscopy Unit, University of Limoges, 87025 Limoges, France, Department of Biology, Faculty of Sciences, Lebanese University, Hadath El Jebbeh, Beyrouth 21219, Lebanon, Doctoral School of Sciences and Technology, Lebanese University, Hadath El Jebbeh, Beyrouth 21219, Lebanon
Published online on: August 27, 2021 https://doi.org/10.3892/mmr.2021.12386
Article Number: 746
Copyright: © Diab et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Natural agents have been used to restart the process of differentiation that is inhibited during leukemic transformation of hematopoietic stem or progenitor cells. Autophagy is a housekeeping pathway that maintains cell homeostasis against stress by recycling macromolecules and organelles and plays an important role in cell differentiation. In the present study, an experimental model was established to investigate the involvement of autophagy in the megakaryocyte differentiation of human erythroleukemia (HEL) cells induced by diosgenin [also known as (25R)‑Spirosten‑5‑en‑3b‑ol]. It was demonstrated that Atg7 expression was upregulated from day 1 of diosgenin‑induced differentiation and was accompanied by a significant elevation in the conversion of light chain 3 A/B (LC3‑A/B)‑I to LC3‑A/B‑II. Autophagy was modulated before or after the induction of megakaryocyte differentiation using 3‑methyladenine (3‑MA, autophagy inhibitor) and metformin (Met, autophagy initiation activator). 3‑MA induced a significant accumulation of the LC3 A/B‑II form at day 8 of differentiation. It was revealed that 3‑MA had a significant repressive effect on the nuclear (polyploidization) and membrane glycoprotein V [(GpV) expression] maturation. On the other hand, autophagy activation increased GpV genomic expression, but did not change the nuclear maturation profile after HEL cells treatment with Met. It was concluded that autophagy inhibition had a more prominent effect on the diosgenin‑differentiated cells than autophagy activation.

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