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The extract selectively targeted cancer cells, triggered apoptosis, and increased reactive oxygen species generation. When combined with dacarbazine at non-toxic concentrations, anticancer activity was enhanced, and pretreatment potentiated the effect of a low dacarbazine dose. 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longifolia Bark Strongly Potentiates the Activity of a Low Dose of Dacarbazine  \nKamila ´Sroda-Pomianek 1,†, Anna Barycka 1,†, Michał Gle ´nsk 2, Meena Rajbhandari 3, Magdalena Skonieczna 4,5, Anna Palko-Łabuz 1,* and Olga Wesołowska 1, *  \nCitation: ´Sroda-Pomianek, K.; Barycka, A.; Gle ´nsk, M.; Rajbhandari, M.; Skonieczna, M.; Palko-Łabuz, A.; Wesołowska, O. Pretreatment of Melanoma Cells with Aqueous Ethanol Extract from Madhuca longifolia Bark Strongly Potentiates the Activity of a Low Dose of Dacarbazine. Int. J. Mol. Sci. 2024, 25, 7220. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms25137220  \nAcademic Editor: Cecilia Garofalo  \nReceived: 24 May 2024  \nRevised: 21 June 2024  \nAccepted: 28 June 2024  \nPublished: 29 June 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Biophysics and Neurobiology, Wroclaw Medical University, 50-369 Wrocław, Poland; [kamila.sroda-pomianek@umw.edu.pl](kamila.sroda-pomianek@umw.edu.pl) (K.´S .-P.); abarycka79@gmail.com (A.B.)  \n2 Department of Pharmacognosy and Herbal Medicines, Wrocław Medical University, 50-367 Wrocław, Poland; [michal.glensk@umw.edu.pl](michal.glensk@umw.edu.pl)  \n3 Research Centre for Applied Science and Technology (RECAST), Kirtipur 44600, Kathmandu, Nepal; [karmacharyameena@gmail.com](karmacharyameena@gmail.com)  \n4 Department of Systems Biology and Engineering, The Silesian University of Technology, 44-100 Gliwice, Poland; [magdalena.skonieczna@polsl.pl](magdalena.skonieczna@polsl.pl)  \n5 Biotechnology Centre, Silesian University of Technology, 44-100 Gliwice, Poland  \n* Correspondence: [anna.palko-labuz@umw.edu.pl](anna.palko-labuz@umw.edu.pl) (A.P.-Ł.); [olga.wesolowska@umw.edu.pl](olga.wesolowska@umw.edu.pl) (O.W.)† These authors contributed equally to this work.  \nAbstract: Madhuca longifolia is an evergreen tree distributed in India, Nepal, and Sri Lanka. This tree is commonly known as Mahua and is used in traditional medicine. It was demonstrated that ethanol extract from the bark of M. longifolia possessed potent cytotoxic activity towards two melanoma cell lines, in contrast to aqueous extract that exhibited no activity. Apart from being selectively cytotoxic to cancer cells (with no activity towards non-cancerous fibroblasts), the studied extract induced apoptosis and increased reactive oxygen species generation in melanoma cells. Additionally, the use of the extract together with dacarbazine (both in non-toxic concentrations) resulted in the enhancement of their anticancer activity. Moreover, the pretreatment of melanoma cells with M. longifolia extract potentiated the activity of a low dose of dacarbazine to an even higher extent. It was concluded that ethanol extract of M. longifolia sensitized human melanoma cells to chemotherapeutic drugs. It can therefore be interesting as a promising source of compounds for prospective combination therapy.  \nKeywords: Madhuca longifolia; bark; ethanol extract; dacarbazine; melanoma; cytotoxicity; potentiation of anticancer activity  \n1. Introduction  \nMadhuca longifolia var. longifolia is an evergreen tree belonging to the family Sapotaceae, distributed in India, Nepal, and Sri Lanka. This tree is commonly known as Mahua and is used traditionally in the treatment of many diseases including rheumatism, epilepsy, ulcers, and inflammations [1,2] . Traditionally the bark of M. longifolia is considered to be beneficial in treating itch, swelling, and bites of poisonous snakes. It has been used internally in diabetes, stomach ulcers, tonsillitis, and pharyngitis [1] . Among act","cbCaijBHDtl1fdsX","https://ap.wps.com/l/cbCaijBHDtl1fdsX","pdf",2633333,16,"English","# Abstract\n# Introduction","[{\"question\":\"What plant material and extracts were tested against melanoma cells?\",\"answer\":\"The study tested aqueous and ethanol extracts from the bark of Madhuca longifolia, evaluating their anticancer effects in human melanoma cell lines.\"},{\"question\":\"How did the ethanol extract compare to the aqueous extract in cytotoxicity?\",\"answer\":\"The ethanol extract strongly limited melanoma cell viability and showed potent cytotoxic activity, whereas the aqueous extract exhibited no activity.\"},{\"question\":\"How did combining the extract with dacarbazine affect anticancer activity?\",\"answer\":\"Using the extract together with dacarbazine in non-toxic concentrations enhanced anticancer activity, and pretreatment further potentiated the activity of a low dose of dacarbazine.\"}]","Pretreatment of Melanoma Cells with Aqueous Ethanol Extract from Madhuca longifolia Bark Strongly Potentiates the Activity of a Low Dose of Dacarbazine | PDF",1789990836]