Quercetin increases mitochondrial proteins (VDAC and SDH) and downmodulates AXL and PIM-1 tyrosine kinase receptors in NRAS melanoma cells

Abstract

Melanoma is a type of skin cancer with low survival rates after it has metastasized. In order to find molecular differences that could represent targets of quercetin in anti-melanoma activity, we have chosen SKMEL-103 and SKMEL-28 melanoma cells and human melanocytes as models. Firstly, we observed that quercetin was able in reducing SKMEL-103 cell viability, but not in SKMEL-28. Besides that, quercetin treatment caused inhibition of AXL in both cell lines, but upregulation of PIM-1 in SKMEL-28 and downregulation in SKMEL-103. Moreover, HIF-1 alpha expression decreased in both cell lines. Interestingly, quercetin was more effective against SKMEL-103 than kinases inhibitors, such as Imatinib, Temsirolimus, U0126, and Erlotinib. Interestingly, we observed that while the levels of succinate dehydrogenase and voltage-dependent anion channel increased in SKMEL-103, both proteins were downregulated in SKMEL-28 after quercetin’s treatment. Furthermore, AKT, AXL, PIM-1, ABL kinases were much more active and chaperones HSP90, HSP70 and GAPDH were highly expressed in SKMEL-103 cells in comparison with melanocytes. Our findings indicate, for the first time, that the efficacy of quercetin to kill melanoma cells depends on its ability in inhibiting tyrosine kinase and upregulating mitochondrial proteins, at least when SKMEL-103 and SKMEL-28 cells response were compared.

Network pharmacology and experiment indicated that medicinal food homologous components play important roles in insomnia

“…We also screened the 10th protein, which is related to Parkinson's syndrome insomnia (PDB code: 1Y7V; Premkumar et al, 2005). Through a literature review, we found that reverse docking with the top nine proteins could directly or indirectly cause insomnia (Duan et al, 2021;Long et al, 2020;Miglis et al, 2021;Orhan, 2021;Rocha-Brito et al, 2022;Romo-Nava et al, 2022; Premkumar et al, 2005) can achieve the effect of treating insomnia.…”

“…We also screened the 10th protein, which is related to Parkinson's syndrome insomnia (PDB code: 1Y7V; Premkumar et al., 2005). Through a literature review, we found that reverse docking with the top nine proteins could directly or indirectly cause insomnia (Duan et al., 2021; Long et al., 2020; Miglis et al., 2021; Orhan, 2021; Rocha‐Brito et al., 2022; Romo‐Nava et al., 2022; Su et al., 2021; Wang et al., 2022; Zhai et al., 2021), and relevant cell experiments or animal experiments have shown that quercetin has an impact on these nine proteins (Ceresa & Peterson, 2014; Cianci et al., 2015; Cuevas et al., 2011; Khodarahmi et al., 2019; Pakdel, 2018; Vieira & Saraiva, 2014). Insomnia is the most immediate symptom experienced by patients with Parkinson's syndrome.…”