| Summary: | <i>Abeliophyllum distichum</i> Nakai, commonly called white forsythia, is a monotypic genus endemic to Korea. Although <i>A. distichum</i> is mainly used as an ornamental plant because of its horticultural value, recent studies have demonstrated its bioactivities, including antioxidant and anti-inflammatory activities, prompting us to investigate the potential anticancer effect of <i>A. distichum</i> organ extracts (leaves, fruit, and branches) against human melanoma SK-MEL-2 cells. The methanol extract of <i>A. distichum</i> leaves (AL) exhibited dose- and time-dependent cytotoxicities against SK-MEL-2 cells but not against HDFa human dermal fibroblasts. Based on high-performance liquid chromatography analysis, we identified 18 polyphenolic compounds from <i>A. distichum</i> organ extracts and suggest that differences in anticancer activity between organ extracts should be caused by different compositions of polyphenolic compounds. Additionally, the Annexin V/propidium iodide staining assay and analysis of caspase activity and expression indicated that AL induced cell death, including early and late apoptosis, as well as necrosis, by inducing the extrinsic pathway. Furthermore, we analyzed the differentially expressed genes between mock- and AL-treated cells using RNA-seq technology, suggesting that the anti-melanoma action of AL is mediated by down-regulation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Taken together, these results shed light on the potential use of <i>A. distichum</i> as a green resource with potent anti-melanoma activity.
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