Bergamottin Induces DNA Damage and Inhibits Malignant Progression in Melanoma by Modulating miR-145/Cyclin D1 Axis

Abstract

Background Melanoma is a prevalent skin cancer with the high rate of metastasis and mortality, affecting the increasing number of people worldwide. Bergamottin (BGM) is a natural furanocoumarin derived from grapefruits and presents the potential anti-cancer activity in several tumor models. However, the role of BGM in the development of melanoma remains unclear. Here, we aimed to explore the effect of BGM on the DNA damage and progression of melanoma. Methods The effect of BGM on the melanoma progression was analyzed by CCK-8 assays, colony formation assays, transwell assays, Annexin V-FITC Apoptosis Detection Kit, cell-cycle analysis, in vivo tumorigenicity analysis. The mechanism investigation was performed using luciferase reporter gene assays, qPCR assays, and Western blot analysis. Results We identified that BGM repressed cell proliferation, migration, and invasion of melanoma cells. BGM induced cell cycle arrest at the G0/G1 phase and enhanced apoptosis of melanoma cells. The DNA damage in the melanoma cells was stimulated by the BGM treatment. Meanwhile, BGM was able to up-regulate the expression of miR-145 and miR-145 targeted Cyclin D1 in the melanoma cells. Furthermore, BGM inhibited the progression of melanoma by targeting miR-145/Cyclin D1 axis in vitro. BGM attenuated the tumor growth of melanoma in vivo. Conclusion Thus, we conclude that BGM induces DNA damage and inhibits tumor progression in melanoma by modulating the miR-145/Cyclin D1 axis. Our finding provides new insights into the mechanism by which BGM modulates the development of melanoma. BGM may be applied as a potential anti-tumor candidate for the clinical treatment of melanoma.

Bergamottin alleviates LPS-induced acute lung injury by inducing SIRT1 and suppressing NF-κB

“… 23 Another study demonstrates that bergamottin evokes DNA damage in melanoma cells. 14 These studies have confirmed the cytotoxic activity of bergamottin in malignant cells. However, bergamottin treatment had mild effect on the viability of non-malignant cells including macrophages and lung epithelial cells ( Supplementary Figure S1 ).…”

“…Previous studies have focused on the anti-cancer effect of bergamottin. 13 , 14 It has been reported that bergamottin causes apoptotic death in tumor cells. 23 Another study demonstrates that bergamottin evokes DNA damage in melanoma cells.…”

“… 12 Bergamottin has attracted increasing interest because of its anti-cancer properties. 13 , 14 It has been reported that bergamottin causes apoptotic death and suppresses proliferation and invasion in melanoma cells. 14 Bergamottin also inhibits metastasis of lung cancer cells.…”

“… 13 , 14 It has been reported that bergamottin causes apoptotic death and suppresses proliferation and invasion in melanoma cells. 14 Bergamottin also inhibits metastasis of lung cancer cells. 15 Most importantly, bergamottin shows the ability to block NF-κB signaling activation.…”

Effects of alcoholic fermentation on the non-volatile and volatile compounds in grapefruit (Citrus paradisi Mac. cv. Cocktail) juice: A combination of UPLC-MS/MS and gas chromatography ion mobility spectrometry analysis

“…Grapefruit encompassed various bioactive chemicals like flavonoids, limonoids, carotenoids, organic acids, pectin, fiber, and folic acid (8)(9)(10)(11). These bioactive substances endow grapefruit with important biomedical activities such as anti-inflammatory, antibacterial, anticancer, chemopreventive, and blood sugar regulation effects (12)(13)(14). Among different grapefruit varieties, "Cocktail" is a special one due to its higher sugar content and lower acidity in comparison with others (15).…”