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

Zara, Rabia; Rasul, Azhar; Sultana, Tayyaba; Jabeen, Farhat; Selamoğlu, Zeliha

doi:10.1016/j.sjbs.2022.02.018

Cited by 15 publications

(9 citation statements)

References 34 publications

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“…Due to its overexpression in some tumors, 6PGD has been identified as a possible therapeutic target for cancer therapy in recent years. 44 In our study, we found a significant increase in lactate and NADPH content in drug-resistant cell lines, and that inhibition of 6PGD reversed such a process. This demonstrated that 6PGD was indispensable in the process of metabolic reprogramming toward epirubicin in TNBC cells, suggesting that upregulated 6PGD was required for NADPH level in epirubicin-resistant cells.…”

Section: Discussionsupporting

confidence: 59%

Inhibition of 6-Phosphogluconate Dehydrogenase Reverses Epirubicin Resistance Through Metabolic Reprograming in Triple-Negative Breast Cancer Cells

Ren

Cheng

2023

Technol Cancer Res Treat

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At present, chemotherapy is the most effective strategy for treating triple-negative breast cancer (TNBC), but its efficacy was limited by the development of chemo-resistance. The exact mechanism of chemoresistance still remains unclear. This study aims to examine whether 6-phosphogluconate dehydrogenase (6PGD), a key enzyme in the oxidative pentose phosphate pathway (PPP), could promote the resistance of TNBC cells to epirubicin. A TNBC epirubicin-resistant cell line was developed by increasing concentration and the effectiveness was tested. The expression and knockdown efficiency of 6PGD were further validated by performing quantitative real-time PCR (qPCR) and Western blot. The effects of 6PGD on parental and drug-resistant TNBC cell lines were verified based on proliferation and apoptosis experiments. Finally, nicotinamide adenine dinucleotide phosphate (NADPH) and lactate quantitative experiments were performed to examine the mechanism of 6PGD in promoting drug resistance. Epirubicin-resistant cancer cells exhibited a higher level of 6PGD in contrast to epirubicin-sensitive cells. In addition, 6PGD inhibited by genetic and pharmacological approaches significantly suppressed the growth and survival of both epirubicin-sensitive and epirubicin-resisteant TNBC cells. It should be noted that 6PGD inhibition sensitized epirubicin-resistant TNBC cells to epirubicin treatment. Moreover, it was also found that the levels of NADPH and lactate increased in epirubicin-resistant TNBC cells but decreased in response to 6PGD inhibition. The present results indicated that 6PGD inhibition disrupted metabolic reprogramming in epirubicin-resistant TNBC cells. Our work demonstrated that 6PGD inhibition reversed the resistance of TNBC cells to epirubicin, providing an alternative therapeutic choice to tackle the challenge of epirubicin resistance in TNBC treatment.

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Section: Discussionsupporting

confidence: 59%

Inhibition of 6-Phosphogluconate Dehydrogenase Reverses Epirubicin Resistance Through Metabolic Reprograming in Triple-Negative Breast Cancer Cells

Ren

Cheng

2023

Technol Cancer Res Treat

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“…The anti-inflammatory activity has partly been attributed to some lanostane-type triterpenoids and cinnamic acid, isolated from the mushroom, inhibiting in vitro NO production in phagocytes [ 20 , 23 ]. Zara et al have found that an 80% ethanolic extract of MP exhibits anticancer activity against A549 lung adenocarcinoma cells with an IC 50 = 6.18 µg/mL, after 24 h of treatment [ 24 ]. The antitumor effect of this mushroom extract has been explained by its inhibitory activity on glucose-6-phosphate dehydrogenase enzyme, which is important for cancer progression.…”

Section: Introductionmentioning

confidence: 99%

Structural Features and Immunomodulatory Effects of Water-Extractable Polysaccharides from Macrolepiota procera (Scop.) Singer

Georgiev

Vašíček

Dzhambazov

et al. 2022

JoF

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Macrolepiota procera (MP) is an edible mushroom used in the treatment of diabetes, hypertension and inflammation. However, the structure and biological effects of its polysaccharides (PSs) are unclear. This study investigates the structural features of a PS complex from MP (MP-PSC), its immunomodulatory activities and effects on probiotic and pathogenic bacteria. MP-PSC was obtained by boiling water, and PSs were characterized by 2D NMR spectroscopy. The immunomodulatory effects on blood and derived neutrophils, other leukocytes, and murine macrophages were studied by flow cytometry, chemiluminescence, spectrophotometry, and ELISA. The total carbohydrate content of MP-PSC was 74.2%, with glycogen occupying 36.7%, followed by β-D-glucan, α-L-fuco-2-(1,6)-D-galactan, and β-D-glucomannan. MP-PSC (200 μg/mL) increased the number of CD14+ monocyte cells in the blood, after ex vivo incubation for 24 h. It dose-dependently (50–200 μg/mL) activated the spontaneous oxidative burst of whole blood phagocytes, NO, and interleukin 6 productions in RAW264.7 cells. MP-PSC exhibited a low antioxidant activity and failed to suppress the oxidative burst and NO generation, induced by inflammatory agents. It (2.0%, w/v) stimulated probiotic co-cultures and hindered the growth and biofilm development of Escherichia coli, Streptococcus mutans and Salmonella enterica. MP PSs can be included in synbiotics to test their immunostimulating effects on compromised immune systems and gut health.

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“…The use of a multi-well plate to measure absorbance at 340 nm is incompatible. Consequently, for G6PD activity a new colorimetric was developed ( Zara et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…Following this, media was aspirated with the addition of 100 µL of DMSO. Finally, using an ELISA plate reader (Thermo Scientific), absorbance was observed at 540 nm wavelength ( Zara et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Smilax china root extract as a novel Glucose- 6-phosphate dehydrogenase inhibitor for the treatment of hepatocellular carcinoma

Kanwal

Ali

Rasul

et al. 2022

Saudi Journal of Biological Sciences

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

Cited by 15 publications

References 34 publications

Inhibition of 6-Phosphogluconate Dehydrogenase Reverses Epirubicin Resistance Through Metabolic Reprograming in Triple-Negative Breast Cancer Cells

Inhibition of 6-Phosphogluconate Dehydrogenase Reverses Epirubicin Resistance Through Metabolic Reprograming in Triple-Negative Breast Cancer Cells

Structural Features and Immunomodulatory Effects of Water-Extractable Polysaccharides from Macrolepiota procera (Scop.) Singer

Smilax china root extract as a novel Glucose- 6-phosphate dehydrogenase inhibitor for the treatment of hepatocellular carcinoma

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