Src inhibition induces melanogenesis in human G361 cells

Ku,Kyung‑Eun; Choi,Nahyun; Oh,Sang‑Ho; Kim,Won‑Serk; Suh,Wonhee; Sung,Jong‑Hyuk

doi:10.3892/mmr.2019.9958

Src inhibition induces melanogenesis in human G361 cells

Authors:
- Kyung‑Eun Ku
- Nahyun Choi
- Sang‑Ho Oh
- Won‑Serk Kim
- Wonhee Suh
- Jong‑Hyuk Sung
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Affiliations: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea, Department of Dermatology, Severance Hospital and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea, Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea, College of Pharmacy, Chung‑Ang University, Seoul 06974, Republic of Korea
Published online on: February 15, 2019 https://doi.org/10.3892/mmr.2019.9958
Pages: 3061-3070
Copyright: © Ku et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Src kinase family (SKF) includes non‑receptor tyrosine kinases that interact with many cellular cytosolic, nuclear and membrane proteins, and is involved in the progression of cellular transformation and oncogenic activity. However, there is little to no evidence on the effect of SKF or its inhibitors on melanogenesis. Therefore, the present study investigated whether C‑terminal Src kinase inhibition can induce melanogenesis and examined the associated signaling pathways and mRNA expression of melanogenic proteins. First, whether stimulators of melanogenesis, such as ultraviolet B and α‑melanocyte‑stimulating hormone, can dephosphorylate Src protein was evaluated, and the results revealed that SU6656 and PP2 inhibited the phosphorylation of Src in G361 cells. Src inhibition by these chemical inhibitors induced melanogenesis in G361 cells and upregulated the mRNA expression levels of melanogenesis‑associated genes encoding microphthalmia‑associated transcription factor, tyrosinase‑related protein 1 (TRP1), TRP2, and tyrosinase. In addition, Src inhibition by small interfering RNA induced melanogenesis and upregulated the mRNA expression levels of melanogenesis‑associated genes. As the p38 mitogen‑activated protein kinase (MAPK) and cyclic adenosine monophosphate response element binding (CREB) pathways serve key roles in melanogenesis, the present study further examined whether Src mediates melanogenesis via these pathways. As expected, Src inhibition via SU6656 or PP2 administration induced the phosphorylation of p38 or CREB, as determined by western blotting analysis, and increased the levels of phosphorylated p38 or CREB, as determined by immunofluorescence staining. In addition, the induced pigmentation and melanin content of G361 cells by Src inhibitors was significantly inhibited by p38 or CREB inhibitors. Taken together, these data indicate that Src is associated with melanogenesis, and Src inhibition induces melanogenesis via the MAPK and CREB pathways in G361 cells.

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