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Published:
Jul 3, 2017DOI:
10.4314/tjpr.v16i6.4Keywords:
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Main Article Content
7-Piperazinethylchrysin inhibits melanoma cell proliferation by targeting Mek 1/2 kinase activity
Abstract
Purpose: To investigate the growth-inhibitory effect of 7-piperazinethylchrysin (PEC) on melanoma cell lines.
Methods: Cell viability was analyzed by trypan blue exclusion assays and the cell cycle by flow cytometry using ModFit LT software. Specifically, cells were stained with propidium iodide (0.5 mg/mL) supplemented with RNase A (50 mg/mL), and analyzed using flow cytometry and ModFit LT software.
Results: In A375 and B16F10 cell cultures, proliferation was reduced to 79 and 72 %, respectively, on treatment with 30 μM PEC. PEC increased the proportion of A375 cells in G1/G0 phase to 71.23 %, versus 42.76 % in untreated cells. In B16F10 and A375 cells, treatment with PEC caused the inhibition of Mek 1/2 kinase activity and suppressed Erk 1/2 phosphorylation. The level of cAMP-response element binding protein was increased by PEC. The expression of microphthalmia-linked transcription factor was also increased by PEC treatment. Marked enhancement was observed in the level of tyrosinase in melanoma cells on treatment with PEC. Analysis of PBG-D expression showed a marked increase in B16F10 and A375 cells on the addition of PEC to cell cultures at 72 h. The level of PBG D expression was increased by 9- and 8.5-fold in B16F10 and A375 cells, respectively, on incubation with 30 μM PEC. The addition of a Mek 1/2 inhibitor (U0126) to the cultures promoted PEC-mediated growth inhibition.
Conclusion: PEC inhibited melanoma cell proliferation, apparently by blocking the cell cycle at G0/G1 and downregulating the Ras/Raf/Mek/Erk pathway.
Keywords: Tyrosinase, Kinase, Microphthalmia, Phosphorylation, 7-Piperazinethylchrysin
