Abstract
Malignant melanoma is developed from pigment-containing cells, melanocytes, and primarily found on the skin. Malignant melanoma still has a high mortality rate, which may imply a lack of therapeutic agents. Lakoochin A, a compound isolated from Artocarpus lakoocha and Artocarpus xanthocarpus, has an inhibitory function of tyrosinase activity and melanin production, but the anti-cancer effects are still unclear. In the current study, the therapeutic effects of lakoochin A with their apoptosis functions and possible mechanisms were investigated on A375.S2 melanoma cells. Several methods were applied, including 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT), flow cytometry, and immunoblotting. Results suggest that lakoochin A attenuated the growth of A375.S2 melanoma cells through an apoptosis mechanism. Lakoochin A first increase the production of cellular and mitochondrial reactive oxygen species (ROSs); mitochondrial ROSs then promote mitogen-activated protein kinases (MAPKs) pathway activation and raise downstream apoptosis-related protein and caspase expression. This is the first study to demonstrate that lakoochin A, through ROS-MAPK, apoptosis-related proteins, caspases cascades, can induce melanoma cell apoptosis and may be a potential candidate compound for treating malignant melanoma.
Highlights
Melanoma is a common form of skin cancer, especially among Caucasians [1]
The results indicate that lakoochin A-induced mitogen-activated protein kinases (MAPKs) pathways activation can be generated by mitochondrial reactive oxygen species (ROSs) in A375.S2 melanoma cells
We first demonstrate that lakoochin A has anti-melanoma cancer cell activity linked to ROS generation and MAPK pathways
Summary
Melanoma is a common form of skin cancer, especially among Caucasians [1]. The malignant form of melanoma, called malignant melanoma, still has a poor prognosis. Several methods, including surgical excision, chemotherapy, radiotherapy, and immunotherapy, have been applied to treat malignant melanoma These treatment methods do not effectively reduce the adverse effects or increase the long-term survival rate [2,3]. For this reason, investigating novel agents or methods to increase the efficacy and prognosis of malignant melanoma treatment are of clinical importance. The functions of lakoochin A have been reported to inhibit α-glucosidase activity [14], melanin biosynthesis [5], antimycobacterial activity against Mycobacterium tuberculosis, and cytotoxicity against breast cancer and nasopharyngeal carcinoma cell lines [4]. The details of lakoochin A on its anti-cancer function and related mechanisms are still unclear and require further investigation
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