Antitumor Activity of Galaxamide Involved in Cell Apoptosis and Stemness by Inhibiting Wnt/β-catenin Pathway in Cervical Cancer.

ABSTRACT: Background and Purpose: Our previous work reported that galaxamide, a cyclopeptide extracted from the seaweed Galaxaura filamentosa, showed antiproliferative activity against HeLa cells by MTT assay. However, the therapeutic effects in vivo and potential mechanisms to eliminate cervical cancer cells remain unknown. Experimental Approach: HeLa cells were obtained as a cervical carcinoma in vitro model. The growth-inhibitory effects of galaxamide in HeLa cells and xenograft mouse models were investigated. RNA-seq was employed to analyse the main target of galaxamide in HeLa cells. Immunostaining, qRT‒PCR and Western blotting were applied to test the pharmacological effects in vitro and in vivo. Key Results: Galaxamide significantly inhibited cell growth, colony formation, migration, and invasion and induced cell apoptosis by inhibiting the Wnt signalling pathway in HeLa cells. RNA sequencing revealed that galaxamide regulated stemness via the Wnt6 signalling pathway in HeLa cells. By analysing The Cancer Genome Atlas database (TCGA), Wnt6 was found to be negatively/positively correlated with stemness- and apoptosis-related genes in human cervical cancer. Cancer stem-like cells (CSCs) isolated and enriched from HeLa cells demonstrated elevated Wnt6 and β-catenin genes compared with nonstem HeLa cells. After galaxamide treatment, CSCs showed abrogation of sphere-forming ability, along with inhibition of stemness-related and Wnt pathway genes. Galaxamide treatment was accompanied by the induction of apoptosis in HeLa cells, which was consistent with the results in BALB/c nude mice. Conclusion and Implications: Our results provide preclinical evidence that suppression of stemness by downregulating the Wnt signalling pathway is the molecular mechanism by which galaxamide effectively inhibits cell growth and induces apoptosis in cervical cancer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228509 | GEO | 2023/04/03

REPOSITORIES: GEO