Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

7-Piperazinethylchrysin inhibits melanoma cell proliferation by targeting Mek 1/2 kinase activity

Ning Zeng¹, Hong Qiu², Xin Lian³, Yuping Ren¹, Yi Xu¹, Yiping Wu¹, Hongbo Tang¹, Haiping Wang¹

¹Department of Plastic and Aesthetic Surgery; ²Department of Oncology; ³Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, China.

For correspondence:- Haiping Wang Email: wanghaiping7@hotmail.com

Received: 18 January 2017 Accepted: 10 May 2017 Published: 29 June 2017

Citation: Zeng N, Qiu H, Lian X, Ren Y, Xu Y, Wu Y, et al. 7-Piperazinethylchrysin inhibits melanoma cell proliferation by targeting Mek 1/2 kinase activity. Trop J Pharm Res 2017; 16(6):1231-1237 doi: 10.4314/tjpr.v16i6.4

© 2017 The authors.
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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