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Hashim 3,4, Yaya Rukayadi 5,6 and Ahmad Faizal Abdull Razis 5,6, *  \nCitation: Eliaser, E.M.; Mohd. Hashim, N.; Rukayadi, Y.; Abdull Razis, A.F. 7-Geranyloxycinnamic Acid Isolated from Melicope  \nlunu-ankenda Leaves Perturbs Colon Cancer and Breast Cancer Cell Lines'Growth via Induction of Apoptotic Pathway. Molecules 2023, 28, 3612 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules28083612  \nAcademic Editor: Hinanit Koltai  \nReceived: 30 October 2022  \nRevised: 30 January 2023  \nAccepted: 30 January 2023  \nPublished: 21 April 2023  \nCopyright: © 2023 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 UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia  \n2 Department of Biology, Faculty of Science, El-Mergib University, El Khums, Libya  \n3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur 50603, Malaysia  \n4 Center of Natural Product Research and Drug Discovery (CENAR), Universiti Malaya, Kuala Lumpur 50603, Malaysia  \n5 Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400, Malaysia  \n6 Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia  \n* [Correspondence: madfaizal@upm.edu.my](Correspondence: madfaizal@upm.edu.my); Tel.: +60-3-97693073  \nAbstract: Globally, breast cancer is the most prevalent form of cancer in women and there is a need for alternative therapies such as plant-derived compounds with low systemic toxicity and selective toxicity to cancer cells. The aim of this study is to assess the cytotoxicity effects of 7-geranyloxycinnamic acid isolated from leaves of Melicope lunu-ankenda, a traditional medicinal plant, on the human breast cancer cell lines. Dried leaf powder was used for the preparation of different crude extracts using different solvents of increasing order of polarity. The structure of the isolated compound from the petroleum ether extract was elucidated by 1H and 13C NMR, LC-MS, and DIP􀀀MS spectroscopy. The cytotoxic activity of the crude extract and 7-geranyloxycinnamic acid analyzed using MTT assay. Apoptotic analysis was evaluated using Annexin V-PI staining, AO/PI staining, intracellular ROS measurement, and measurement of activities of caspases 3/7, 8, and 9 . Crude extracts and the isolated pure compound showed significant cytotoxicity against tested cancer cell lines. 7-geranyloxycinnamic acid was found to exert significant cytotoxic effects against breast cancer cell lines such as the MCF-7 and MDA-MB-231 cell lines. The cytotoxic effects are attributed to its ability to induce apoptosis via accumulation of ROS and activation of caspasesin both breast cancer cell lines. The pure compound, 7-geranyloxycinnamic acid isolated from the leaves of M. lunu-ankenda, can exert significant cytotoxic effects against breast cancer cell lines without affecting the normal cells.  \nKeywords: cancer; Melicope lunu-ankenda; 7-geranyloxycinnamic acid; cytotoxicity  \n1. Introduction  \nBreast cancer is a serious public health concern in both developed and developing nations and it is the most frequent cause of cancer-related deaths in women [1] . The incidence and the mortality rates of breast cancer have increased in the last few decades. According to the Global Estimates of Cancer (GLOBOCAN) 2020, breast cancer is the first most","cbCaigfY6MvbsSXA","https://ap.wps.com/l/cbCaigfY6MvbsSXA","pdf",10491071,38,"English","# Abstract\n# Keywords\n# 1. Introduction\n## Breast cancer background and treatment challenges\n## Rationale for phytotherapy","[{\"question\":\"What is the main goal of the study?\",\"answer\":\"To evaluate the cytotoxic effects of 7-geranyloxycinnamic acid isolated from Melicope lunu-ankenda leaves on human breast cancer cell lines.\"},{\"question\":\"How was the isolated compound identified and characterized?\",\"answer\":\"The structure of the isolated compound was elucidated using 1H and 13C NMR, LC-MS, and DIP-MS spectroscopy.\"},{\"question\":\"What mechanisms explain the cytotoxic effects on breast cancer cells?\",\"answer\":\"Cytotoxicity is attributed to induction of apoptosis through ROS accumulation and activation of caspases in the tested breast cancer cell lines.\"}]","7-Geranyloxycinnamic Acid Isolated from Melicope lunu-ankenda Leaves Perturbs Colon Cancer and Breast Cancer Cell Lines' Growth via Induction of Apoptotic Pathway | PDF",1790243481,96]