Sanggenon O induced apoptosis of A549 cells is counterbalanced by protective autophagy |
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| Affiliation: | 1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;2. Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;3. Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj, Saudi Arabia;4. Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt;1. Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India;2. Department of Dermatology and Venereology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India;3. Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India;1. Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India;2. Department of Pharmacology, College of Pharmacy, Jazan University, PO Box 114, Gizan, Saudi Arabia;3. Department of Chemistry, College of Science and Humanities, Prince Sattam bin Abdulaziz University, P.O. Box- 173, Al-Kharj, Saudi Arabia;4. The Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India;1. Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran;2. Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;1. Dipartimento di Farmacia, Università “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy;2. Affichem S.A., 9 Rue Saint Joseph, 31400 Toulouse, France;3. Cholesterol Metabolism and Therapeutic Innovations, Cancer Research Center of Toulouse (CRCT), UMR 1037, Université de Toulouse, CNRS, Inserm, Toulouse, France |
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| Abstract: | Sanggenon O (SO) is a Diels-Alder type adduct extracted from Morus alba, which has been used for its anti-inflammatory action in the Oriental medicine. However, whether it has regulatory effect on human cancer cell proliferation and what the underlying mechanism remains unknown. Here, we found that SO could significantly inhibit the growth and proliferation of A549 cells and induce its pro-apoptotic action through a caspase-dependent pathway. It could also impair the mitochondria which can be reflected by mitochondrial membrane permeabilization. Besides, SQSTM1 up-regulation and autophagic flux measurement demonstrated that exposure to SO led to autophagosome accumulation, which plays a protective role in SO-treated cells. In addition, knocking down of LC3B increased SO triggered apoptotic cell rates. These results indicated that SO has great potential as a promising candidate combined with autophagy inhibitor for the treatment of NSCLC. In conclusion, our results identified a novel mechanism by which SO exerts potent anticancer activity. |
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| Keywords: | Sanggenon O Non-small cell lung cancer Cell proliferation Autophagosome Apoptosis SQSTM1" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" sequestosome 1 LC3B" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" microtubule-associated protein 1 light chain 3 beta SO" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" Sanggenon O MTT" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide EdU" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" 5-ethynyl-20-deoxyuridine MDC" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" monodansylcadaverine PBS" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" phosphate-buffered saline PAGE" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" polyacrylamide gel CQ" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" chloroquine Baf" },{" #name" :" keyword" ," $" :{" id" :" k0125" }," $$" :[{" #name" :" text" ," _" :" bafilomycin A1 |
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