The interplay of p38 MAPK signaling and mitochondrial metabolism, a dynamic target in cancer and pathological contexts

Sarg, Nadin H.; Zaher, Dana M.; Abu Jayab, Nour N.; Mostafa, Salma H.; Ismail, Hussein H.; Omar, Hany A.

doi:10.1016/j.bcp.2024.116307

Biochemical Pharmacology

2024

DOI: 10.1016/j.bcp.2024.116307

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The interplay of p38 MAPK signaling and mitochondrial metabolism, a dynamic target in cancer and pathological contexts

Nadin H. Sarg,

Dana M. Zaher,

Nour N. Abu Jayab

et al.

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2024

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Cited by 3 publications

References 173 publications

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BHLHE40-mediated transcriptional activation of GRIN2D in gastric cancer is involved in metabolic reprogramming

Liu,

Sun,

Wang

et al. 2024

Funct Integr Genomics

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BHLHE40-mediated transcriptional activation of GRIN2D in gastric cancer is involved in metabolic reprogramming

Liu,

Sun,

Wang

et al. 2024

Funct Integr Genomics

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The journey of p38 MAP kinase inhibitors: From bench to bedside in treating inflammatory diseases

Yang,

Zhao,

et al. 2024

European Journal of Medicinal Chemistry

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Comprehensive Analysis of NADH:Ubiquinone Oxidoreductase Subunit B3 in Gynecological Tumors and Identification of Its Natural Inhibitor Wedelolactone

Li,

Jin,

Zhang

et al. 2024

Chem Biol Drug Des

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The aim of this study was to explore the role of NADH:ubiquinone oxidoreductase subunit B3 (NDUFB3) in human gynecological malignancies and to screen potential natural compounds targeting it. GEPIA and HPA databases were used to study the expression characteristics of NDUFB3. GO and KEGG enrichment analyses were performed using the R software clusterProfiler package. GSEA for NDUFB3 was performed using the LinkedOmics database. Natural compounds targeting NDUFB3 were screened by virtual screening and molecular docking. After NDUFB3 was depleted or wedelolactone treatment, cell proliferation was detected by CCK‐8 assay. The production of reactive oxide species (ROS) in tumor cells was detected by dihydroethidium fluorescent probe. The cell cycle and apoptosis were evaluated by flow cytometry. It was revealed that NDUFB3 was highly expressed in ovarian cancer (OV), uterine corpus endometrial carcinoma (UCEC), and cervical squamous cell carcinoma (CESC). NDUFB3 expression was associated with multiple immunomodulators in CESC, OV, and UCEC. NDUFB3 was predicted to modulate MAPK signaling pathways in CESC, OV, and UCEC. Knocking down NDUFB3 inhibited the proliferation of CESC, OV, and UCEC cells, increased intracellular ROS production, and induced cell cycle arrest and apoptosis. Wedelolactone was a potential small molecule with a strong ability to bind with the active pocket of NDUFB3, and wedelolactone could kill CESC, OV, and UCEC cells partly via NDUFB3. In conclusion, NDUFB3 may be a potential biomarker and a new target for gynecological tumors, and wedelolactone may exert antitumor activity via targeting NDUFB3.

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The interplay of p38 MAPK signaling and mitochondrial metabolism, a dynamic target in cancer and pathological contexts

Cited by 3 publications

References 173 publications

BHLHE40-mediated transcriptional activation of GRIN2D in gastric cancer is involved in metabolic reprogramming

BHLHE40-mediated transcriptional activation of GRIN2D in gastric cancer is involved in metabolic reprogramming

The journey of p38 MAP kinase inhibitors: From bench to bedside in treating inflammatory diseases

Comprehensive Analysis of NADH:Ubiquinone Oxidoreductase Subunit B3 in Gynecological Tumors and Identification of Its Natural Inhibitor Wedelolactone

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