Induction of melanogenesis by 4′-O-methylated flavonoids in B16F10 melanoma cells

Abstract

Agents to control melanogenesis are in demand for the development of cosmetics to improve pigmentation disorders of skin and hair. In this study, we examined and evaluated the effects of flavonoids on melanogenesis in the melanogenic cells model, murine B16F10 melanoma cells. In the course of this study, we found that incubation of the cells in a medium containing 10 μM of the 4'-O-methylated flavonoids, diosmetin (4'-O-methylluteolin), acacetin (4'-O-methylapigenin) or kaempferide (4'-O-methylkaempferol), increased the melanin contents of the cells 3- to 7-fold higher than the control cells. The concentration-dependence test revealed that 20 μM acacetin showed the highest effect, up to 33-fold higher than the vehicle. On the other hand, the corresponding 4'-OH-type flavonoids, luteolin, apigenin and kaempferol, had a significantly smaller effect. Furthermore, by evaluating the melanogenic proteins, we found that the cells treated with 4'-O-methylated flavonoids showed higher tyrosinase activity, as well as upregulation of tyrosinase expression, preceded by activation of cAMP response element binding protein (CREB) and extracellular signal-regulated kinases types 1 and 2 (ERK1/2). These results indicate that the 4'-O-methyl group of flavonoids plays an important role in the induction of melanogenesis by activating its major signal transduction pathway through the upregulation of phospho-CREB in murine B16F10 melanoma cells.

Flavonoids activating adenosine monophosphate-activated protein kinase

“…It increases the melanin content in B16F10 melanoma cells (Horibe et al 2013). Even though its activation of AMPK has not been reported, it is known to increase glucose uptake activity (Ueda et al 2013); thus, supporting the current result that kaempferide activates the phosphorylation of AMPK.…”

Phytochemicals for the Management of Melanoma

“…It has been found to inhibit angiogenesis, promote apoptosis, and sensitize cells to anti-cancer therapy in a variety of malignancies [342]. The compound was found to induce melanogenesis and reduce invasive potential of B16F10 melanoma cells by decreasing EMT through inhibition of the β3 integrin/FAK signal pathway [343–345]. Luteolin protected DNA, inhibited cell cycle progression and promoted apoptosis in A375 melanoma cells in a different investigation [346–348].…”

Kazakh Ziziphora Species as Sources of Bioactive Substances

“…[39] Toxicity against Artemia salina larvae [62] Antiradical [63] Weak antibacterial effect [61] OH OCH3 OCH3 OCH3 OH H Acacetin (5) Z. clinopodioides [39] Low vasorelaxant activity (IC50 not calc.) [39] Inhibition of angiogenesis [64,65] Induction of apoptosis in different cancer cell lines [66][67][68][69][70] Inhibition of TNF-related apoptosis [71] Anticancer [72,73] Induction of melanogenesis in B16F10 cells [74] Cytotoxic against HL-60 cells cells [75] Interaction with telomeres [76] Antimetastatic effect [77,78] Diosmetin (6) Z. clinopodioides [4] Some inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4] Cytotoxic against HL-60 cells cells [75] Induction of melanogenesis in B16F10 cells [73,74] Review on bioactivity [79] H OH H OH OCH 3 H Diosmin (7) Z. clinopodioides [80] Antidiabetic activity (reviewed by Abdurrazak et al [81]) Review on clinical use [82] H O-Glc-Rha H OH OCH 3 Hf Linarin (8) Z. clinopodioides [44,80] Inhibition of mucin production and secretion in airways epithelial cells [83] Hepatoprotective [84] Potential inhibitor of CDK4 in retinoblastoma [85] Neuroprotective [86] Inhibition of acetylcholinesterase [87] Anti-inflammatory [88]...…”

“…Induction of melanogenesis in B16F10 cells [73,74] Review on bioactivity [79] Diosmin (7) Z. clinopodioides [80] Antidiabetic activity (reviewed by Abdurrazak et al [81]) Review on clinical use [82] H O-Glc-Rha H OH OCH3 Hf…”