Dihydrocapsaicin Inhibits Cell Proliferation and Metastasis in Melanoma via Down-regulating β-Catenin Pathway

Frontiers in Oncology

Chaowei Deng¹  Chongyang Li¹  Hongjuan Cui¹  Shaomin Shi²  Yanli Zhang³  Juan Du³  Yaling Liu³  Lichao Liu³  Qian Li³  Leiyang Guo³  Wei Liu³  Huanrong Hu³  Yacong Ji³ 

[1] Cancer Center, Medical Research Institute, Southwest University, Chongqing, China;Department of Dermatology, Fifth Hospital of Shijiazhuang, Shijiazhuang, China;Department of Dermatology, Third Hospital of Hebei Medical University, Shijiazhuang, China;State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China;

关键词: dihydrocapsaicin;    melanoma;    cell proliferation;    metastasis;    β-catenin;    ubiquitination;   

DOI  :  10.3389/fonc.2021.648052

来源: DOAJ

【 摘 要 】

Dihydrocapsaicin (DHC) is one of the main components of capsaicinoids in Capsicum. It has been reported that DHC exerts anti-cancer effects on diverse malignant tumors, such as colorectal cancer, breast cancer, and glioma. However, studies focused on the effect of DHC upon melanoma have rarely been done. In the present study, melanoma A375 and MV3 cell lines were treated with DHC and the cell proliferation, migration, and invasion were significantly suppressed. Furthermore, DHC effectively inhibited xenograft tumor growth and pulmonary metastasis of melanoma cells in NOD/SCID mice model. It was identified that β-catenin, which plays significant roles in cell proliferation and epithelial-mesenchymal transition, was down-regulated after DHC treatment. In addition, cyclin D1, c-Myc, MMP2, and MMP7, which are critical in diverse cellular process regulation as downstream proteins of β-catenin, were all decreased. Mechanistically, DHC accelerates ubiquitination of β-catenin and up-regulates the beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) in melanoma cells. The DHC induced suppression of cell proliferation, migration, and invasion were partly rescued by exogenous β-catenin overexpression, both in vitro and in vivo. Taken together, DHC may serve as a candidate natural compound for human melanoma treatment through β-catenin pathway.

【 授权许可】

Unknown