TY - JOUR
T1 - Icariin induces cell differentiation and cell cycle arrest in mouse melanoma B16 cells via Erk1/2-p38-JNK-dependent pathway
AU - Wang, Dan
AU - Xu, Wenjuan
AU - Chen, Xiaoyu
AU - Han, Jichun
AU - Yu, Lina
AU - Gao, Caixia
AU - Hao, Wenjin
AU - Liu, Xiaona
AU - Zheng, Qiusheng
AU - Li, Defang
N1 - Funding Information:
Zheng and 81602556 to Defang Li), the Scientific Research Foundation of Binzhou Medical University (BY2014KYQD01 to Qiusheng Zheng, BY2016KYQD01 to Defang Li and BY2014KYQD30 to Wenjin Hao), the Innovative Team Areas of Key Areas of Xinjiang Production and Construction Corps (2015BD005 to Qiusheng Zheng) and the Dominant Disciplines’ Talent Team Development Scheme of Higher Education of Shandong Province (to Defang Li).
Funding Information:
This study was supported by the National Natural Science Foundation of China (31471338 to Qiusheng
PY - 2017/8/10
Y1 - 2017/8/10
N2 - 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 ICAtreated 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.
AB - 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 ICAtreated 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.
KW - B16 cells
KW - Cell-cycle arrest
KW - Differentiation
KW - Erk1/2-p38-JNK-dependent pathway
KW - Icariin
UR - http://www.scopus.com/inward/record.url?scp=85034638562&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.20118
DO - 10.18632/oncotarget.20118
M3 - Journal article
AN - SCOPUS:85034638562
SN - 1949-2553
VL - 8
SP - 99504
EP - 99513
JO - Oncotarget
JF - Oncotarget
IS - 59
ER -