Icariin induces cell differentiation and cell cycle arrest in mouse melanoma B16 cells via Erk1/2-p38-JNK-dependent pathway.

Dan Wang,Wenjuan Xu,Defang Li,Lina Yu,Xiaoyu Chen,Caixia Gao,Jichun Han,Wenjin Hao,Xiaona Liu,Qiusheng Zheng

doi:10.18632/oncotarget.20118

Abstract

Icariin (ICA) is a major component isolated from Epimedium brevicornum. Emerging evidence shows that ICA can inhibit tumor cell proliferation, invasion and migration. However, the anti-cancer effect of ICA on B16 cells has not been fully investigated. Here we found that the proliferation of B16 cells was inhibited by ICA in a concentration- and time-dependent manner, and the colony formation of B16 cells was also inhibited by ICA in a concentration-dependent manner. Further study showed that the melanin content was increased and the tyrosinase (Tyr) activity was enhanced after ICA treatment in B16 cells. Furthermore, compared with the control group, the mRNA levels of Tyr, Trp1 and Trp2 and the protein level of MITF were increased in ICA-treated B16 cells. In addition, the percentage of G0/G1 phase cells was increased and the protein levels of Cyclin A, CDK2 and p21 were decreased in ICA-treated B16 cells. Finally, we found that ICA increased down-regulated the Erk1/2, p-Erk1/2, p38, p-p38, and p-JNK protein levels in B16 cells when compared with the control group. Taken together, these results indicated that ICA could induce B16 cell differentiation and cell cycle arrest at G0/G1 phase through inhibiting Erk1/2-p38-JNK-dependent signaling molecules.

Highlights

Melanoma, as the most serious skin cancer, is often considered one of the most aggressive human cancers [1]
These results indicated that ICA could induce B16 cell differentiation and cell cycle arrest at G0/G1 phase through inhibiting Erk1/2-p38JNK-dependent signaling molecules
The results suggest that the p38 Mitogen Activated Protein Kinases (MAPK) signaling pathway was involved in the melanogenesis of apigenin, that the activation of p38 MAPK and the upregulation of microphthalmia-associated transcription factor (MITF) contribute to the melanogenesis of apigenin in B16 cells [8]

Summary

Introduction

As the most serious skin cancer, is often considered one of the most aggressive human cancers [1]. Melanoma is the most common malignant tumor in skin tumors, which is prone to distant metastasis [2]. The survival rate of melanoma patients has been greatly improved and its incidence is rapidly increasing throughout the world, especially in the United States, the number of people newly diagnosed with melanoma has increased over the last 10 years [3]. Melanoma cells can survive in extreme environmental conditions and it is characterized by genomic instability, cutaneous melanomas are often difficult to treat when diagnosed in advanced stages [5]. Primary melanoma has a high cure rate in early diagnosis of surgical resection, the survival rate of patients with visceral metastases is only a few months. The discovery of new therapeutic agents and melanoma drug targets has become the urgent matter

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Conclusion