Identification of Macrolepiota procera extract as a novel G6PD inhibitor for the treatment of lung cancer

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dc.authoridSelamoglu, Zeliha/0000-0001-9056-6435
dc.contributor.authorZara, Rabia
dc.contributor.authorRasul, Azhar
dc.contributor.authorSultana, Tayyaba
dc.contributor.authorJabeen, Farhat
dc.contributor.authorSelamoglu, Zeliha
dc.date.accessioned2024-11-07T13:31:36Z
dc.date.available2024-11-07T13:31:36Z
dc.date.issued2022
dc.departmentNiğde Ömer Halisdemir Üniversitesi
dc.description.abstractTumor metabolism, an emerging hallmark of cancer, is characterized by aberrant expression of enzymes from various metabolic pathways including glycolysis and PPP (pentose phosphate pathway). Glucose 6 phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD), oxidative carboxylases of PPP, have been reported to accomplish different biosynthetic and energy requirements of cancer cells. G6PD and 6PGD have been proposed as potential therapeutic targets for cancer therapy during recent years due to their overexpression in various cancers. Here, we have employed enzymatic assay based screening using in-house G6PD and 6PGD assay protocols for the identification of mushroom extracts which could inhibit G6PD or 6PGD enzymatic activity for implications in cancer therapy. For the fulfillment of the objectives of present study, nine edible mushrooms were subjected to green extraction for preparation of ethanolic extracts. 6xhis-G6PD and pET-28a-h6PGD plasmids were expressed in BL21-DE3 E. coli cells for the expression and purification of protein of interests. Using purified proteins, in house enzymatic assay protocols were established. The preliminary screening identified two extracts (Macrolepiota procera and Terfezia boudieri) as potent and selective G6PD inhibitors, while no extract was found highly active against 6PGD. Further, evaluation of anticancer potential of mushroom extracts against lung cancer cells revealed Macrolepiota procera as potential inhibitor of cancer cell proliferation with IC50 value of 6.18 lg/ml. Finally, screening of M. procera-derived compounds against G6PD via molecular docking has identified paraben, quercetin and syringic acid as virtual hit compounds possessing good binding affinity with G6PD. The result of present study provides novel findings for possible mechanism of action of M. procera extract against A549 via G6PD inhibition suggesting that M. procera might be of therapeutic interest for lung cancer treatment.(c) 2022 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.description.sponsorshipNRPU Research Grant [8381/Punjab/NRPU/RD/HEC/2017, 8382/Punjab/NRPU/R D/HEC/2017]; ISESCO awarded Research Grant 2018
dc.description.sponsorshipThis study was supported by the grants from the NRPU Research Grant (8381/Punjab/NRPU/R&D/HEC/2017), (8382/Punjab/NRPU/R &D/HEC/2017) and ISESCO awarded Research Grant 2018.
dc.identifier.doi10.1016/j.sjbs.2022.02.018
dc.identifier.endpage3379
dc.identifier.issn1319-562X
dc.identifier.issn2213-7106
dc.identifier.issue5
dc.identifier.pmid35865797
dc.identifier.scopus2-s2.0-85125459450
dc.identifier.scopusqualityQ1
dc.identifier.startpage3372
dc.identifier.urihttps://doi.org/10.1016/j.sjbs.2022.02.018
dc.identifier.urihttps://hdl.handle.net/11480/14941
dc.identifier.volume29
dc.identifier.wosWOS:000794858400003
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofSaudi Journal of Biological Sciences
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20241106
dc.subjectEdible mushrooms
dc.subjectLung cancer
dc.subjectGlucose 6-phosphate (G6PD)
dc.subjectMacrolepiota procera
dc.titleIdentification of Macrolepiota procera extract as a novel G6PD inhibitor for the treatment of lung cancer
dc.typeArticle

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