{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T09:29:04Z","timestamp":1786440544024,"version":"build-2736575974"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Previous studies have examined bioactive constituents of Prunus dulcis oil, Pinus sylvestris essential oil, and related phytochemical matrices separately; however, their combined chemical profile, comparator-context molecular-docking landscape, and comparative cellular response in melanoma and non-malignant fibroblast models remain insufficiently characterized. Methods: The analyzed study samples were profiled by GC\/MS and GC\/FID-based fatty-acid methyl ester analysis. An archived molecular-docking dataset was used to summarize structurally plausible interactions of six formulation-associated markers with eight melanoma-relevant or melanoma-adjacent targets and to present representative three-dimensional complexes. Because complete protocol metadata and co-crystallized-ligand redocking records were unavailable, the computational findings were interpreted descriptively. Neutral-red uptake assays assessed the 24 h viability of B16F10 melanoma cells and MRC-5 fibroblasts after exposure to each oil, the dual-oil formulation, or cisplatin. Four-parameter logistic models provided estimated IC50 values, and exact two-sided permutation tests were used for Spearman rank analyses. Results: The dual-oil formulation yielded estimated IC50 values of 1.42% v\/v in B16F10 cells and 4.85% v\/v in MRC-5 cells, corresponding to an apparent selectivity index of 3.41. The complete eight-concentration series was non-monotonic and showed no significant rank association (B16F10: \u03c1s = \u22120.4286, exact p = 0.2992; MRC-5: \u03c1s = \u22120.3810, exact p = 0.3599). In a post hoc analysis of the descending branch (\u22650.37% v\/v), the association was perfect in B16F10 cells (\u03c1s = \u22121.0000, exact p = 0.0167) but did not reach significance in MRC-5 cells (\u03c1s = \u22120.9000, exact p = 0.0833). The docking matrix identified target-dependent numerical prioritization patterns; however, small score differences were not interpreted as evidence of stronger binding or cellular target engagement. Conclusions: The findings define an exploratory chemical\u2013computational\u2013cellular framework and a preliminary formulation-level viability phenotype. They do not establish synergy, apoptosis, pathway modulation, therapeutic efficacy, or clinical safety. Independent multi-batch chemical confirmation, a fully documented and redocking-validated computational protocol, expanded melanoma and normal-skin cell panels, orthogonal functional assays, longer exposure periods, mechanistic validation, and subsequent in vivo studies are required.<\/jats:p>","DOI":"10.3390\/life16081314","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:09:36Z","timestamp":1786435776000},"page":"1314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Chemical, Computational, and Cellular Profiling of a Dual-Oil Melanoma Formulation: An Exploratory Life-Science Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Katarina","family":"Dunjic","sequence":"first","affiliation":[{"name":"Discipline of Dermato-Venereology, Quince Medic Clinic, Bulevar Oslobodjenja 2, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8594-0135","authenticated-orcid":false,"given":"Momir","family":"Dunjic","sequence":"additional","affiliation":[{"name":"Discipline of Obstetrics\/Gynecology and Integrative Medicine, Faculty of Medicine, University of Pristina, Anri Dinana bb, 38220 Kosovska Mitrovica, Serbia"},{"name":"Faculty of Pharmacy, Heroja Pinkija 4, 21000 Novi Sad, Serbia"},{"name":"Department of Physical Medicine, Alma Mater Europaea (AMEU-ECM), Slovenska Ulica 17, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-9004","authenticated-orcid":false,"given":"Marina","family":"Gazdic Jankovic","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5177-1521","authenticated-orcid":false,"given":"Marina","family":"Miletic Kovacevic","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-7414","authenticated-orcid":false,"given":"Nikolina","family":"Kastratovic","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-2720","authenticated-orcid":false,"given":"Biljana","family":"Ljujic","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Novakovic","sequence":"additional","affiliation":[{"name":"Discipline of Internal Medicine, Faculty of Medicine, University of Pristina, Anri Dinana bb, 38220 Kosovska Mitrovica, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9976-1472","authenticated-orcid":false,"given":"Milan","family":"Filipovic","sequence":"additional","affiliation":[{"name":"Surgery Department, Discipline of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Pristina, Anri Dinana bb, 38220 Kosovska Mitrovica, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Filipovic","sequence":"additional","affiliation":[{"name":"Discipline of Anatomy, Faculty of Medicine, University of Pristina, Anri Dinana bb, 38220 Kosovska Mitrovica, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Jing","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences (CACMS), Dongcheng District, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Dunjic","sequence":"additional","affiliation":[{"name":"Discipline of Plastic and Reconstructive Surgery, Quince Medic Clinic, Bulevar Oslobodjenja 2, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3300-6199","authenticated-orcid":false,"given":"Miroslav M.","family":"Sovrli\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3761-823X","authenticated-orcid":false,"given":"Sandra S.","family":"Konstantinovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Technology, University of Ni\u0161, 16000 Leskovac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7923-0770","authenticated-orcid":false,"given":"Jelena S.","family":"Stanojevi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Technology, University of Ni\u0161, 16000 Leskovac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan D.","family":"Kosti\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Technology, University of Ni\u0161, 16000 Leskovac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4466-4530","authenticated-orcid":false,"given":"Stefano","family":"Turini","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine, Alma Mater Europaea (AMEU-ECM), Slovenska Ulica 17, 2000 Maribor, Slovenia"},{"name":"Division of Advanced Research and Development, Worldwide Consultancy and Services, Via Andrea Ferrara 45, 00165 Rome, Italy"},{"name":"Division of Environmental Medicine and Security, Capri Campus Forensic and Security, Via G. Orlandi 91, 80071 Anacapri, Italy"},{"name":"Pancic Institute for Research on Medicinal Plants, Institute of Medical Research, University of Belgrade, Dr Suboti\u0107a 4, 11029 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wellbrock, C., and Arozarena, I. (2016). The Complexity of the ERK\/MAP-Kinase Pathway and the Treatment of Melanoma Skin Cancer. Front. Cell Dev. Biol., 4.","DOI":"10.3389\/fcell.2016.00033"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Savoia, P., Fava, P., Casoni, F., and Cremona, O. (2019). Targeting the ERK Signaling Pathway in Melanoma. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061483"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Patel, M., Eckburg, A., Gantiwala, S., Hart, Z., Dein, J., Lam, K., and Puri, N. (2021). Resistance to Molecularly Targeted Therapies in Melanoma. Cancers, 13.","DOI":"10.3390\/cancers13051115"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e70566","DOI":"10.1002\/mco2.70566","article-title":"Melanoma: Pathogenesis and Targeted Therapy","volume":"7","author":"Fu","year":"2026","journal-title":"MedComm"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1038\/s41416-021-01565-w","article-title":"Quantifying ERK activity in response to inhibition of the BRAFV600E-MEK-ERK cascade using mathematical modelling","volume":"125","author":"Hamis","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kosnopfel, C., Sinnberg, T., Mane, S., Dongo, M., Garbe, C., and Niessner, H. (2025). Combinatorial ERK Inhibition Enhances MAPK Pathway Suppression in BRAF-Mutant Melanoma. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199794"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41698-024-00684-w","article-title":"Efficacy of PARP inhibitor therapy after targeted BRAF\/MEK failure in advanced melanoma","volume":"8","author":"Phillipps","year":"2024","journal-title":"npj Precis Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kim, H.-D., Choi, H., Abekura, F., Park, J.-Y., Yang, W.-S., Yang, S.-H., and Kim, C.-H. (2023). Naturally-Occurring Tyrosinase Inhibitors Classified by Enzyme Kinetics and Copper Chelation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098226"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Baber, M.A., Crist, C.M., Devolve, N.L., and Patrone, J.D. (2023). Tyrosinase Inhibitors: A Perspective. Molecules, 28.","DOI":"10.3390\/molecules28155762"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cardoso, R., Valente, R., Souza da Costa, C.H., Vianez, J.L.d.S.G., da Costa, K.S., de Molfetta, F.A., and Alves, C.N. (2021). Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach. Molecules, 26.","DOI":"10.3390\/molecules26102875"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1040693","DOI":"10.1155\/2022\/1040693","article-title":"Molecular Docking, Synthesis, and Tyrosinase Inhibition Activity of Acetophenone Amide: Potential Inhibitor of Melanogenesis","volume":"2022","author":"Nazir","year":"2022","journal-title":"BioMed Res. Int."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Namieci\u0144ska, E., Jaszczak, J., Hikisz, P., Da\u015bko, M., Wo\u017aniczka, M., and Budzisz, E. (2025). Evaluation of Tyrosinase Inhibitory Activity of Carbothioamidopyrazoles and Their Potential Application in Cosmetic Products and Melanoma Treatment. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083882"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1534735419845139","DOI":"10.1177\/1534735419845139","article-title":"A Fragrant Environment Containing alpha-Pinene Suppresses Tumor Growth in Mice by Modulating the Hypothalamus\/Sympathetic Nerve\/Leptin Axis and Immune System","volume":"18","author":"Kusuhara","year":"2019","journal-title":"Integr. Cancer Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.bbrc.2011.06.176","article-title":"Alpha-Pinene isolated from Schinus terebinthifolius Raddi induces apoptosis and confers antimetastatic protection in a melanoma model","volume":"411","author":"Matsuo","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1089\/jmf.2023.K.0267","article-title":"Anticancer Effects of alpha-Pinene in AGS Gastric Cancer Cells","volume":"27","author":"Han","year":"2024","journal-title":"J. Med. Food"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41420-021-00510-3","article-title":"Antitumor effect of Melaleuca alternifolia essential oil and its main component terpinen-4-ol in combination with target therapy in melanoma models","volume":"7","author":"Garzoli","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4278","DOI":"10.1038\/s41598-025-34538-7","article-title":"Alpha-Terpineol induces apoptosis in melanoma cells and its underlying mechanism","volume":"16","author":"Liu","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chu, M.-H., Hsiao, S.-W., Kao, Y.-C., Yin, H.-W., Kuo, Y.-H., and Lee, C.-K. (2022). Cytotoxicity Effect of Constituents of Pinus taiwanensis Hayata Twigs on B16-F10 Melanoma Cells. Molecules, 27.","DOI":"10.3390\/molecules27092731"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S290","DOI":"10.4103\/0973-1296.166052","article-title":"Selectivity of Pinus sylvestris extract and essential oil to estrogen-insensitive breast cancer cells","volume":"11","author":"Nguyen","year":"2015","journal-title":"Pharmacogn. Mag."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.3892\/ijo.2011.1263","article-title":"Pinus densiflora leaf essential oil induces apoptosis via ROS generation and activation of caspases in YD-8 human oral cancer cells","volume":"40","author":"Jo","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"476","DOI":"10.4103\/1735-5362.194887","article-title":"Cytotoxic effects of Pinus eldarica essential oil and extracts on HeLa and MCF-7 cell lines","volume":"11","author":"Sarvmeili","year":"2016","journal-title":"Res. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1080\/13880209.2017.1296003","article-title":"Fatty acid composition and anticancer activity in colon carcinoma cell lines of Prunus dulcis seed oil","volume":"55","author":"Mericli","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"433","DOI":"10.12688\/f1000research.131336.3","article-title":"Assessing the cytotoxicity of phenolic and terpene fractions extracted from Iraqi Prunus arabica against AMJ13 and SK-GT-4 human cancer cell lines","volume":"12","author":"Mahmood","year":"2024","journal-title":"F1000Research"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ben Khadher, T., Sassi-Aydi, S., Aydi, S., Mars, M., and Bouajila, J. (2023). Phytochemical Profiling and Biological Potential of Prunus dulcis Shell Extracts. Plants, 12.","DOI":"10.20944\/preprints202306.0680.v1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.18632\/oncotarget.26930","article-title":"Frankincense essential oil suppresses melanoma cancer through down regulation of Bcl-2\/Bax cascade signaling and ameliorates hepatotoxicity via phase I and II drug metabolizing enzymes","volume":"10","author":"Hakkim","year":"2019","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nanni, V., Di Marco, G., Sacchetti, G., Canini, A., and Gismondi, A. (2020). Oregano Phytocomplex Induces Programmed Cell Death in Melanoma Lines via Mitochondria and DNA Damage. Foods, 9.","DOI":"10.3390\/foods9101486"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s10616-012-9499-1","article-title":"Galangin induces B16F10 melanoma cell apoptosis via mitochondrial pathway and sustained activation of p38 MAPK","volume":"65","author":"Zhang","year":"2013","journal-title":"Cytotechnology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Massaoka, M.H., Matsuo, A.L., Figueiredo, C.R., Farias, C.F., Girola, N., Arruda, D.C., Scutti, J.A.B., Romoff, P., Favero, O.A., and Ferreira, M.J.P. (2012). Jacaranone Induces Apoptosis in Melanoma Cells via ROS-Mediated Downregulation of Akt and p38 MAPK Activation and Displays Antitumor Activity In Vivo. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038698"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhao, W., Chen, Z., Fu, W., Ye, C., Fu, H., Xu, T., Wu, B., Chen, L., and Shan, S.-J. (2025). Induction of apoptosis and hypoxic stress in malignant melanoma cells via graphene-mediated far-infrared radiation. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-14031-0"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12986-019-0365-4","article-title":"Dietary compounds and cutaneous malignant melanoma: Recent advances from a biological perspective","volume":"16","author":"Ombra","year":"2019","journal-title":"Nutr. Metab."},{"key":"ref_31","first-page":"591","article-title":"Anticancer activity of essential oils and their chemical components\u2014A review","volume":"4","author":"Bayala","year":"2014","journal-title":"Am. J. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"953451","DOI":"10.1155\/2014\/953451","article-title":"Antitumor Activity of Monoterpenes Found in Essential Oils","volume":"2014","author":"Sobral","year":"2014","journal-title":"Sci. World J."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mohamed Abdoul-Latif, F., Ainane, A., Houmed Aboubaker, I., Mohamed, J., and Ainane, T. (2023). Exploring the Potent Anticancer Activity of Essential Oils and Their Bioactive Compounds. Pharmaceuticals, 16.","DOI":"10.3390\/ph16081086"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"392674","DOI":"10.1155\/2015\/392674","article-title":"Antitumor Phenylpropanoids Found in Essential Oils","volume":"2015","author":"Carvalho","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Dumitras, D.-A., and Andrei, S. (2022). Recent Advances in the Antiproliferative and Proapoptotic Activity of Various Plant Extracts and Constituents against Murine Malignant Melanoma. Molecules, 27.","DOI":"10.3390\/molecules27082585"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tabolacci, C., De Vita, D., Facchiano, A., Bozzuto, G., Beninati, S., Failla, C.M., Di Martile, M., Lintas, C., Mischiati, C., and Stringaro, A. (2023). Phytochemicals as Immunomodulatory Agents in Melanoma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032657"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kim, H.J., and Hong, J.H. (2024). Multiplicative Effects of Essential Oils and Other Active Components on Skin Tissue and Skin Cancers. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105397"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.canlet.2013.02.056","article-title":"Emerging phytochemicals for prevention of melanoma invasion","volume":"335","author":"Jones","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1111\/php.12749","article-title":"Melanoma Chemoprevention: Current Status and Future Prospects","volume":"93","author":"Chhabra","year":"2017","journal-title":"Photochem. Photobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1039\/C4NP00130C","article-title":"Natural products with therapeutic potential in melanoma metastasis","volume":"32","author":"AlQathama","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Isacescu, E., Chiroi, P., Zanoaga, O., Nutu, A., Budisan, L., Pirlog, R., Atanasov, A.G., and Berindan-Neagoe, I. (2023). Melanoma Cellular Signaling Transduction Pathways Targeted by Polyphenols Action Mechanisms. Antioxidants, 12.","DOI":"10.3390\/antiox12020407"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Benedusi, M., Lee, H., Lim, Y., and Valacchi, G. (2024). Oxidative State in Cutaneous Melanoma Progression: A Question of Balance. Antioxidants, 13.","DOI":"10.3390\/antiox13091058"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ruzzolini, J., Peppicelli, S., Andreucci, E., Bianchini, F., Scardigli, A., Romani, A., La Marca, G., Nediani, C., and Calorini, L. (2018). Oleuropein has an anti-cancer effect on human BRAF melanoma cells and potentiates cytotoxicity of current chemotherapies. Nutrients, 10.","DOI":"10.3390\/nu10121950"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2565084","DOI":"10.1155\/jskc\/2565084","article-title":"Phytochemicals From Houttuynia cordata Thunb as Potential Inhibitors of BRAF, MEK, and ERK: Insights From Molecular Docking","volume":"2025","author":"Yanarojana","year":"2025","journal-title":"J. Skin. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"38339","DOI":"10.1038\/s41598-025-22320-8","article-title":"Computational and pharmacophore-based study of Camellia sinensis phytochemicals targeting BRAF in melanoma","volume":"15","author":"Shuvo","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Furlan, V., Ravnik, V., Bren, U., and Jukic, M. (2026). Insights into Molecular Mechanisms of Polyphenolic Compounds from Helichrysum italicum by Inverse Molecular Docking Fingerprint Approach. Pharmaceuticals, 19.","DOI":"10.3390\/ph19040647"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.canlet.2015.01.016","article-title":"Targeting Drivers of Melanoma with Synthetic Small Molecules and Phytochemicals","volume":"359","author":"Strickland","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"953","DOI":"10.2174\/1389557516666160211120157","article-title":"Phytochemicals for the Management of Melanoma","volume":"16","author":"Pal","year":"2016","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/med.21880","article-title":"Skin cancer, related pathways and therapy and the role of luteolin derivatives as potential therapeutics","volume":"42","author":"Juszczak","year":"2022","journal-title":"Med. Res. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Singaravelan, N., and Tollefsbol, T.O. (2025). Polyphenol-Based Prevention and Treatment of Cancer Through Epigenetic and Combinatorial Mechanisms. Nutrients, 17.","DOI":"10.3390\/nu17040616"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Tomko, A.M., Whynot, E.G., Ellis, L.D., and Dupr\u00e9, D.J. (2020). Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis. Cancers, 12.","DOI":"10.3390\/cancers12071985"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Hundsberger, H., Stierschneider, A., Sarne, V., Ripper, D., Schimon, J., Weitzenb\u00f6ck, H.P., Schild, D., Jacobi, N., Eger, A., and Atzler, J. (2021). Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids. Molecules, 26.","DOI":"10.3390\/molecules26030717"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Cho, M.-K., Lee, Y., Kim, K.D., Choi, M.H., Lee, S.-H., Choi, D., Nam, H.-S., and Lee, Y.-J. (2026). Dietary Polyphenols Curcumin and Resveratrol Exert Selective Anticancer Effects in Melanoma Cells. Nutrients, 18.","DOI":"10.3390\/nu18030548"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"34128","DOI":"10.1021\/acsomega.4c05123","article-title":"Comparative Study of Essential Oils from Tunisian Pinus halepensis by Hydrodistillation and Microwave-Assisted Processes","volume":"9","author":"Hamzaoui","year":"2024","journal-title":"ACS Omega"},{"key":"ref_55","first-page":"133","article-title":"Effects of pine needle essential oil on melanin synthesis in B16F10 cells and its mechanism","volume":"23","author":"Shang","year":"2025","journal-title":"BioMed Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Thalappil, M.A., Butturini, E., de Prati, A.C., Bettin, I., Antonini, L., Sapienza, F.U., Garzoli, S., Ragno, R., and Mariotto, S. (2022). Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells. Molecules, 27.","DOI":"10.3390\/molecules27154834"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00432-023-05572-7","article-title":"Natural products targeting the MAPK-signaling pathway in cancer: Overview","volume":"150","author":"Shi","year":"2024","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e02536","DOI":"10.1002\/cbdv.202502536","article-title":"The Potential of Phytochemicals to Overcome Multidrug Resistance in Metastatic Melanoma","volume":"23","author":"Maphutha","year":"2025","journal-title":"Chem. Biodivers."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kowalski, S., Karska, J., Tota, M., Skinderowicz, K., Kulbacka, J., and Drag-Zalesinska, M. (2024). Natural Compounds in Non-Melanoma Skin Cancer: Prevention and Treatment. Molecules, 29.","DOI":"10.3390\/molecules29030728"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Babashpour-Asl, M., Yousefpour-Dokhanieh, A., and Farajzadeh-Memari-Tabrizi, E. (2025). Evaluation of nutritional and antioxidant properties of almond cultivars: A comprehensive analysis for health and industry applications. BMC Plant Biol., 25.","DOI":"10.1186\/s12870-025-07626-z"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s00217-025-04681-6","article-title":"Evaluation of pomological traits and fatty acid profile of almond (Prunus dulcis L. [Mill.] D.A. Webb) genotypes grown in Yozgat province","volume":"251","year":"2025","journal-title":"Eur. Food Res. Technol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/aocs.12941","article-title":"Integrated impact of environmentally friendly extraction and recovery methods on almond oil quality: Insights from a lipidomic perspective","volume":"102","author":"Dias","year":"2025","journal-title":"J. Am. Oil Chem. Soc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"852","DOI":"10.3844\/ojbsci.2025.852.859","article-title":"Comparative phytochemical analysis of hydrodistilled essential oils of Scots pine (Pinus sylvestris L.) needles from Central Kazakhstan","volume":"25","author":"Tuleshova","year":"2025","journal-title":"OnLine J. Biol. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Mirkovi\u0107, S., Martinovi\u0107, M., Tadi\u0107, V.M., Ne\u0161i\u0107, I., Jovanovi\u0107, A.S., and \u017dugi\u0107, A. (2025). Antimicrobial and antioxidant activity of essential oils from selected Pinus species from Bosnia and Herzegovina. Antibiotics, 14.","DOI":"10.3390\/antibiotics14070677"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:34:52Z","timestamp":1786437292000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":64,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["life16081314"],"URL":"https:\/\/doi.org\/10.3390\/life16081314","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}