Abstract
Abeliophyllum distichum Nakai, commonly called white forsythia, is a monotypic genus endemic to Korea. Although A. distichum 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 A. distichum organ extracts (leaves, fruit, and branches) against human melanoma SK-MEL-2 cells. The methanol extract of A. distichum 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 A. distichum 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 A. distichum as a green resource with potent anti-melanoma activity.
Highlights
Malignant melanoma is the deadliest skin cancer type that originates from pigment-producing cells known as melanocytes [1]
(48.091 ± 12.741%) strongly inhibited the proliferation of SK-MEL-2 cells compared with A. distichum branches (AB) (84.229 ± 7.335%) and A. distichum fruits (AF) (86.949 ± 6.287%), 200 μg/ml of all extracts showed similar cytotoxic activity
Chemotherapeutic agents, including irinotecan, doxorubicin, oxaliplatin, and cyclophosphamide, have shown promising results alone or in combination with other cancer therapies, their unexpected activities against normal cells have led to harmful side effects [13]
Summary
Malignant melanoma is the deadliest skin cancer type that originates from pigment-producing cells known as melanocytes [1]. It is caused by multiple and progressive DNA damage related to proto-oncogene activation, down-regulation of tumor suppressor genes, and structural changes of the chromosomes [2]. Since malignant melanomas have been treated by surgical removal, cryosurgery, radiation therapy, or chemotherapy, there has been a growing interest in the use of complementary and alternative medicines because of the disadvantages mediated by conventional cancer chemotherapies and the health benefits of phytochemicals [5]. The functional diversity of phytochemicals should provide unique and renewable resources to discover and develop potential new antitumor agents, suggesting that the investigation of biological and pharmaceutical properties of medicinal plants and their natural products is an important issue in the development of complementary or adjunctive therapies
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