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    Cancer metabolism regulation by phytonutrients
    (Elsevier, 2022) Riaz, Ammara; Zara, Rabia; Bushra, Gul; Kanwal, Nazia; Sadiqa, Ayesha; Shareef, Farzana; Sarfraz, Iqra
    In spite of the advanced researches, preventive measures, and treatment options, cancer remains a growing ailment all over the world and its prevalence is estimated to increase in future. Cellular metabolic alterations have been documented as a hallmark of cancer. Metabolic regulation is an intricately coupled process whose deregulation leads to tumor progression as well as metastasis. In order to thrive in the living system, cancer cells adapt different metabolic pathways (bioenergetics and biosynthesis). They replenish their metabolic demands by switching from normal metabolism to cancer metabolism by the process of metabolic rewiring. Recent researches suggest that starving cancer cells by the use of nontoxic chemical entities can give promising results regarding cancer proliferation. Natural products, especially those of plant origin, offer different chemical scaffolds to target cancer via modulation of multiple cell signaling cascades. Phytonutrients, the secondary metabolites from the plants, constitute edible phytochemicals which are abundantly found in vegetables, whole grains, and fruits. The growing numbers of evidences suggest that phytonutrients exhibit anticancer as well as chemopreventive activities of these bioactive molecules against several cancers by targeting the various significant enzymes of glycolysis, the PPP pathway, TCA cycle, and serine metabolism. This book chapter presents an update for the scientific community about targeting the cancer metabolism by phytonutrients. The alterations in the cancer metabolism in the context of bioenergetics, biosynthesis, and mitochondrial functions have been discussed while presenting the impact of phytonutrients as modulators of potential metabolic effectors in the cancer metabolism. © 2022 Elsevier Inc. All rights reserved.
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    Identification of Macrolepiota procera extract as a novel G6PD inhibitor for the treatment of lung cancer
    (Elsevier, 2022) Zara, Rabia; Rasul, Azhar; Sultana, Tayyaba; Jabeen, Farhat; Selamoglu, Zeliha
    Tumor 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/).