RT Journal Article SR Electronic T1 Naringenin Induces Cellular Apoptosis in Melanoma Cells via Intracellular ROS Generation JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1079 OP 1086 DO 10.21873/anticanres.16903 VO 44 IS 3 A1 FERNANDO, PINCHA DEVAGE SAMEERA MADUSHAN A1 ZHEN, AO XUAN A1 PIAO, MEI JING A1 HERATH, HERATH MUDIYANSELAGE UDARI LAKMINI A1 KANG, KYOUNG AH A1 YOON, SANG-PIL A1 BOO, HYE-JIN A1 HYUN, CHANG LIM A1 HYUN, JIN WON YR 2024 UL http://ar.iiarjournals.org/content/44/3/1079.abstract AB Background/Aim: Melanoma is a prevalent malignant tumor that arises from melanocytes. The treatment of malignant melanoma has become challenging due to the development of drug resistance. It is, therefore, imperative to identify novel therapeutic drug candidates for controlling malignant melanoma. Naringenin is a flavonoid abundant in oranges and other citrus fruits and recognized for its numerous medicinal benefits. The objective of the study was to assess the anti-carcinogenic potential of naringenin by evaluating its ability to regulate the cellular production of reactive oxygen species (ROS) and its effect on mitochondrial function and apoptosis in melanoma cells. Materials and Methods: Cell viability, intracellular ROS levels, cell apoptosis, and mitochondrial functions were evaluated. Results: Naringenin decreased melanoma cell viability and triggered generation of ROS, leading to cell apoptosis. In addition, it stimulated mitochondrial damage in melanoma cells by elevating the levels of Ca2+ and ROS in the mitochondria and decreasing cellular ATP. Naringenin stimulated the expression of proapoptotic proteins, including phospho p53, B-cell lymphoma-2 (Bcl-2)-associated X protein, cleaved caspase-3, and cleaved caspase-9, in melanoma cells in a time-dependent manner. Furthermore, it reduced the expression of the anti-apoptotic protein Bcl-2. Naringenin triggered cell apoptosis by phosphorylating c-Jun N-terminal kinase and stimulating cellular autophagy. Conclusion: Naringenin caused oxidative stress and mitochondrial damage, and activated autophagy in melanoma cells, leading to cell apoptosis. These findings indicate the potential of naringenin as a new therapeutic candidate for melanoma.