Naringenin enhances anti-proliferation effect of 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one on two different cells via targeting calmodulin signaling pathway

Rajabi, Sadegh; Noori, Shokoofe; Ashrafi, Mandana; Movahed, Mahsa Azami; Farzaneh, Shabnam; Zarghi, Afshin

doi:10.1007/s11033-021-06923-8

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“…However, this observation is inconsistent with our model of the upregulation of let-7g by NGN-attenuated KRAS–PI3K–Rac1–Akt axis metabolic functions, probably because the study cited used a hepatoma cell that conferred the cell-type specificity of miRNA expression to post-translational regulation of the expression of PI3K–Akt-regulated mRNAs involved in metabolism. Studies from chronic myelogenous leukemia [ 63 ], breast cancer [ 64 ], colon cancer [ 65 ], and glioblastoma cells [ 66 ] showed the pharmacological activities of NGN by targeting multiple signal pathways, indicating that NGN could differentially modulate the expression of cellular genes that are involved in cell growth, apoptosis, and cell invasion in different types of cancer cells. Although NGN induced let-7g expression and decreased KRAS, apoptosis and bioenergetic dysfunction were not observed in the S-G cells.…”

Section: Discussionmentioning

confidence: 99%

Let-7g Upregulation Attenuated the KRAS–PI3K–Rac1–Akt Axis-Mediated Bioenergetic Functions

Hung,

Tien,

Bau

et al. 2023

Cells

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The aberrant activation of signaling pathways contributes to cancer cells with metabolic reprogramming. Thus, targeting signaling modulators is considered a potential therapeutic strategy for cancer. Subcellular fractionation, coimmunoprecipitation, biochemical analysis, and gene manipulation experiments revealed that decreasing the interaction of kirsten rat sarcoma viral oncogene homolog (KRAS) with p110α in lipid rafts with the use of naringenin (NGN), a citrus flavonoid, causes lipid raft-associated phosphatidylinositol 3-kinase (PI3K)−GTP-ras-related C3 botulinum toxin substrate 1 (Rac1)−protein kinase B (Akt)-regulated metabolic dysfunction of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), leading to apoptosis in human nasopharyngeal carcinoma (NPC) cells. The use of lethal-7g (let-7g) mimic and let-7g inhibitor confirmed that elevated let-7g resulted in a decrease in KRAS expression, which attenuated the PI3K−Rac1−Akt−BCL-2/BCL-xL-modulated mitochondrial energy metabolic functions. Increased let-7g depends on the suppression of the RNA-specificity of monocyte chemoattractant protein-induced protein-1 (MCPIP1) ribonuclease since NGN specifically blocks the degradation of pre-let-7g by NPC cell-derived immunoprecipitated MCPIP1. Converging lines of evidence indicate that the inhibition of MCPIP1 by NGN leads to let-7g upregulation, suppressing oncogenic KRAS-modulated PI3K–Rac1–Akt signaling and thereby impeding the metabolic activities of aerobic glycolysis and mitochondrial OXPHOS.

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