Cyanidin-3-o-Glucoside Pharmacologically Inhibits Tumorigenesis via Estrogen Receptor β in Melanoma Mice

: Mei Liu, Yaqi Du, Haiwen Li, Li Wang, Donata Ponikwicka-Tyszko, Weronika Lebiedzinska, Agata Pilaszewicz-Puza, Huijiao Liu, Lijun Zhou, Hanlu Fan, Mingming Wang, Hua You, Slawomir Wolczynnski, Nafis Rahman, Yang-Dong Guo, Xiangdong Li

Publisher: Frontiers Editorial Office

: 2019

: Frontiers in Oncology

: Frontiers in oncology

: Front Oncol

: 110

: 9

: 18

: 2234-943X

DOI: https://doi.org/10.3389/fonc.2019.01110

: https://www.frontiersin.org/articles/10.3389/fonc.2019.01110/full

: https://research.utu.fi/converis/portal/detail/Publication/44660097

Expression patterns of estrogen receptors [ERα, ERβ, and G-protein
associated ER (GPER)] in melanoma and skin may suggest their
differential roles in carcinogenesis. Phytoestrogenic compound
cyanidin-3-o-glucoside (C3G) has been shown to inhibit the growth and
metastatic potential of melanoma, although the underlying molecular
mechanism remains unclear. The aim of this study was to clarify the
mechanism of action of C3G in melanoma in vitro and in vivo, as well as to characterize the functional expressions of ERs in melanoma. In normal skin or melanoma (n
= 20/each), no ERα protein was detectable, whereas expression of ERβ
was high in skin but weak focal or negative in melanoma; and finally
high expression of GPER in all skin vs. 50% melanoma tissues (10/20) was
found. These results correspond with our analysis of the melanoma
survival rates (SRs) from Human Protein Atlas and The Cancer Genome
Atlas GDC (362 patients), where low ERβ expression in melanoma correlate with a poor relapse-free survival, and no correlations were observed between SRs and ERα or GPER
expression in melanoma. Furthermore, we demonstrated that C3G treatment
arrested the cell cycle at the G2/M phase by targeting cyclin B1
(CCNB1) and promoted apoptosis via ERβ in both mouse and human melanoma
cell lines, and inhibited melanoma cell growth in vivo. Our study
suggested that C3G elicits an agonistic effect toward ERβ signaling
enhancement, which may serve as a potential novel therapeutic and
preventive approach for melanoma.

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