Enggar Yusrina Hasyyati, Maftuchah Rochmanti, Nafhah, Adha Fauzi Hendrawan, Arifa Mustika, Happy Kurnia Permatasari, Gioconda Millotti, Fahrul Nurkolis
Background: Melanoma is one of the deadliest forms of skin cancer, with rising incidence and limited responsiveness to conventional chemotherapy. Marine macroalgae have recently emerged as a promising source of novel bioactive compounds with potential anticancer properties. Objective: This study aimed to investigate the anticarcinogenic and antioxidant potential of Hydropuntia edulis extract (HEE) using integrated metabolomic profiling, in silico predictions, and in vitro validation against melanoma. Methods: Untargeted LC-HRMS metabolomic profiling was conducted to identify bioactive constituents in HEE. Key compounds were further analyzed through structure–activity relationship (SAR), ADMET, and molecular docking simulations targeting melanoma-related proteins (BRAF, AKT1, EGFR, and TYRO3). Antioxidant and antiproliferative effects were assessed using DPPH and MTT assays on B16-F10 melanoma cells. Results: Several metabolites including Sangivamycin, Michosterol C, Linamarin, and Elaiomycin K were identified. SAR analysis showed high antineoplastic probability for Linamarin (Pa = 0.831), Sangivamycin (Pa = 0.730), and Michosterol C (Pa = 0.759). Michosterol C showed strong binding affinity to BRAF (−9.2 kcal/mol), comparable to Dabrafenib (−9.1 kcal/mol). HEE demonstrated dose-dependent DPPH radical scavenging and inhibited melanoma cell proliferation with IC50 values similar to positive controls. Conclusion: This study highlights Hydropuntia edulis as a promising source of nutraceutical agents against melanoma. Through a combination of metabolomic profiling, computational prediction, and in vitro testing, HEE was shown to contain multiple bioactive compounds with antioxidant and antiproliferative potential. These findings suggest HEE could be further developed as a dietary supplement or functional food to support nutritional management of melanoma patients, rather than as a stand-alone chemotherapeutic. Future studies including compound isolation, in vivo validation, and clinical trials are needed to clarify its relevance, optimal dosing, and safety profile. © 2025 Sociedad espanola de dietetica. All rights reserved.
Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Pharmacology, Faculty of Medicine, Muhammadiyah University of Surabaya, Indonesia; Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; Department of Biochemistry and Biomolecular, Faculty of Medicine, Brawijaya University, Malang, Indonesia; Faculty of Natural Sciences, Juraj Dobrila University of Pula, Pula, Croatia; State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, Indonesia; Medical Research Center of Indonesia (MRCI), Surabaya, Indonesia
