The dietary flavonoid isoliquiritigenin induced apoptosis and suppressed metastasis in melanoma cells: An in vitro and in vivo study

• Published in: Life sciences (1973) Vol. 264; p. 118598
• Main Authors: Xiang, Shijian, Zeng, Haiyan, Xia, Fan, Ji, Qiufeng, Xue, Jianwen, Ren, Ruxia, Que, Fuchang, Zhou, Benjie
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2021; Elsevier BV
• Subjects: Animals; Anticancer properties; Antitumor activity; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Assaying; c-Myc protein; Cell Line, Tumor; Cell migration; Cell proliferation; Chalcones - administration & dosage; Diet; Ectopic expression; Female; Flavonoids; Flavonoids - administration & dosage; Flow cytometry; Gene expression; Gene set enrichment analysis; Homeobox; Humans; In vivo methods and tests; Isoliquiritigenin; Kinases; Melanoma; Melanoma - drug therapy; Melanoma - pathology; Melanoma, Experimental - drug therapy; Melanoma, Experimental - pathology; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; miR-27a; Myc protein; p53 Protein; Signal transduction; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Tissue analysis; Tumor cell lines; Wound healing; Xenograft Model Antitumor Assays - methods; Xenografts; Xenotransplantation; Isoliquiritigenin; miR-27a; Metastasis; Melanoma; Apoptosis
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118598

This study aimed to explore the role of Isoliquiritigenin (ISL) in the proliferation and invasion of melanoma cells and investigate the mechanism of action of this compound. The functional roles of ISL in melanoma cells were determined by CCK8 assay, colony formation assay, flow cytometry and wound healing assay. The antitumor activity of ISL was assessed in vivo in a mouse xenograft model using A2058 cells. Quantitative real-time PCR analysis (RT-qPCR) and western blot assays were used to evaluate the gene and protein expression in cell lines or tumor tissue samples. Bioinformatic analysis, luciferase reporter assay, and gene set enrichment analysis (GSEA) were performed to confirm the mechanism of ISL effect on cell growth and metastasis of melanoma. ISL suppressed proliferation and migration of melanoma cells via downregulation of miR-27a expression. The inhibitory effect of ISL on growth and metastasis of melanoma cells was reversed by ectopic expression of miR-27a. Bioinformatic analysis showed that miR-27a targets POU class 2 homeobox 3 (POU2F3); this result was verified by the luciferase reporter assay and by a decrease in the expression of POU2F3 by miR-27a intervention. GSEA demonstrated that POU2F3 is associated with the c-MYC/p53 signaling pathway and metastasis. POU2F3 knockdown reversed the inhibitory effect of ISL on the growth and metastasis of melanoma. Additionally, POU2F3 was found to be downregulated in melanoma tissue samples and was negatively correlated with miR-27a. ISL inhibits proliferation and metastasis of melanoma via the miR-27a/POU2F3/c-MYC/p53 axis; these results may provide a new thought for the treatment of melanoma.