Effects of Quercetin, Kaempferol, and Exogenous Glutathione on Phospho- and Total-AKTin 3T3-L1 Preadipocytes

Abstract

Obesity has been reported to be a risk factor for some types of cancer, such as prostate and lung. The AKT or PI3K-AKT is a signal transduction pathway that promotes survival and growth in response to extracellular signals. The aim of this study was to investigate the effects of two flavonoids, quercetin and kaempferol, and exogenous glutathione (GSH) on the expressions of phospho- and total-AKT levels in 3T3-L1 preadipocytes. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) levels were measured in the treated samples and used as the internal standard. 3T3-L1 preadipocytes were exposed to each flavonoid and GSH at concentrations of 0, 5, 10, 15, 20, and 25 µM, and the levels of phospho- and total-Akt were measured by the MILLIPLEX MAP mates protocol, based on the Luminex xMAP technology (Millipore Corp., St. Charles, MI, USA). GAPDH levels in the preadipocytes were not significantly different at the doses tested for the flavonoids and exogenous GSH. However, significant (p <.05) decreases in phospho-AKT levels in cells treated with quercetin, kaempferol, and GSH at certain doses were observed compared to their respective controls. Total-AKT levels showed the same profile for all the tested compounds. Significant (p <.01) differences were observed for kaempferol (15-25 µM), quercetin at 10 and 20 µM, and GSH at 10 µM compared to their respective controls. Findings suggest that exposure of 3T3-L1 preadipocytes to quercetin, kaempferol, and GSH may block the activation of AKT, suggesting the role such compounds play in cell differentiation in 3T3-L1 cells.

Flavonoids as antiobesity agents: A review

“…146 Likewise, quercetin blocked adipocyte differentiation via inhibition of MAPK and PI3K/Akt pathways, reducing the BW in almost 40% of HFD-obese mice when compared with nontreated controls. 166,167 Finally, previous reports have revealed that plasma lipid and cholesterol levels have a strong relationship with the hypertrophic adipocyte phenotype. 35 Typical dyslipidemia in obesity is characterized by increased levels of TGs and FFAs, decreased HDL cholesterol with HDL dysfunction, and normal or slightly increased LDL cholesterol with increased small dense LDL, as cholesterol and TGs cannot circulate freely in the bloodstream (see Figure 1).…”

Kaempferol: A Key Emphasis to Its Anticancer Potential

“…Lung cancer, such as non-small-cell lung cancer, displays a poor prognosis and is currently contributing to increasing the number of cancer-related deaths worldwide [89]. Kaempferol concentration dependently prevented the growth of lung adenocarcinoma A549 cells [90,91,92,93], decreased colony formation, and triggered apoptosis [94]. Kaempferol also markedly prevented cell migration, recovered the loss of E-cadherin, and suppressed EMT [89].…”

“…Kaempferol also markedly prevented cell migration, recovered the loss of E-cadherin, and suppressed EMT [89]. Kaempferol still downregulated the expression of claudin-2, AKT/PI3K phosphorylation, ERK pathways, Bcl-2, Bcl-xL, MEK1/2, MMP2, tissue inhibitor of metalloproteinases 2 (TIMP2), MAPK and up-regulated the expression of Bax, Fas, cleaved-caspase-3,-7,-8,-9, AIF (caspase-independent), and miR-340 transcription, involved in the apoptosis pathway [90,91,92,93,94,95]. In a lung metastasis model, kaempferol was also able to reduce the volume of subcutaneous xenograft and the number of metastasis compared to the control group [94].…”

Dual Substrate Specificity of the Rutinosidase from Aspergillus niger and the Role of Its Substrate Tunnel

“…Rutinosidase is used in the food industry for taste and aroma improvement of tea or wine or for citrus juice debittering [ 5 ]. Quercetin and hesperetin have been proven to have anti-inflammatory and antioxidative effects [ 6 , 7 , 8 , 9 ]. Rutinosidases can be applied in the manufacturing of dietary supplements and bioactive products that contain these flavonoids.…”