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Targeting akt/mtor and bcl‐2 for autophagic and apoptosis cell death in lung cancer: Novel activity of a polyphenol compound
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Document Title
Targeting akt/mtor and bcl‐2 for autophagic and apoptosis cell death in lung cancer: Novel activity of a polyphenol compound
Author
Tungsukruthai S.,Reamtong O.,Roytrakul S.,Sukrong S.,Vinayanwattikun C.,Chanvorachote P.
Name from Authors Collection
Affiliations
Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand; Cell‐Based Drug and Health Products Development Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand; Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, 12120, Thailand; Research Unit of DNA Barcoding of Thai Medicinal Plants, Chulalongkorn University, Bangkok, 10330, Thailand; Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand
Type
Article
Source Title
Antioxidants
ISSN
20763921
Year
2021
Volume
10
Issue
4
Open Access
All Open Access, Gold
Publisher
MDPI
DOI
10.3390/antiox10040534
Abstract
Autophagic cell death (ACD) is an alternative death mechanism in resistant malignant cancer cells. In this study, we demonstrated how polyphenol stilbene compound PE5 exhibits po-tent ACD‐promoting activity in lung cancer cells that may offer an opportunity for novel cancer treatment. Cell death caused by PE5 was found to be concomitant with dramatic autophagy induc-tion, as indicated by acidic vesicle staining, autophagosome, and the LC3 conversion. We further confirmed that the main death induction caused by PE5 was via ACD, since the co‐treatment with an autophagy inhibitor could reverse PE5‐mediated cell death. Furthermore, the defined mechanism of action and upstream regulatory signals were identified using proteomic analysis. Time-dependent proteomic analysis showed that PE5 affected 2142 and 1996 proteins after 12 and 24 h of treatment, respectively. The crosstalk network comprising 128 proteins that control apoptosis and 25 proteins involved in autophagy was identified. Protein–protein interaction analysis further indicated that the induction of ACD was via AKT/mTOR and Bcl‐2 suppression. Western blot analysis confirmed that the active forms of AKT, mTOR, and Bcl‐2 were decreased in PE5‐treated cells. Taken together, we demonstrated the novel mechanism of PE5 in shifting autophagy toward cell death induction by targeting AKT/mTOR and Bcl‐2 suppression. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Keyword
AKT/mTOR | Apoptosis | Autophagic cell death | Autophagy | Bcl‐2 | lung cancer | Polyphenol | Proteomics | Stilbene compounds
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
Chulalongkorn University
License
CC BY
Rights
Author
Publication Source
Scopus