Terpenoids from Leaves of Guarea macrophylla Display In Vitro Cytotoxic Activity and Induce Apoptosis In Melanoma Cells.

Conserva, Geanne Alexandra A, Girola, Natalia, Figueiredo, Carlos R, Azevedo, Ricardo A ORCID: 0000-0003-4381-797X, Mousdell, Sasha, Sartorelli, Patricia ORCID: 0000-0002-1624-8145, Soares, Marisi G, Antar, Guilherme M ORCID: 0000-0001-8109-4544 and Lago, João Henrique G ORCID: 0000-0002-1193-8374
(2017) Terpenoids from Leaves of Guarea macrophylla Display In Vitro Cytotoxic Activity and Induce Apoptosis In Melanoma Cells. Planta medica, 83 (16). 1289 - 1296.

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<i>Guarea macrophylla</i> is a Brazilian plant species that has been used in folk medicine to treat a range of diseases. Our ongoing work focuses on the discovery of new bioactive natural products derived from Brazilian flora. The current study describes the identification of cytotoxic compounds from the EtOH extract of leaves from <i>G. macrophylla</i> using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of four compounds: cycloart-23<i>E</i>-ene-3<i>β</i>,25-diol (<b>1</b>), (23<i>S</i>*,24<i>S</i>*)-dihydroxycicloart-25-en-3-one (<b>2</b>), isopimara-7,15-diene-2<i>α</i>,3<i>β</i>-diol (<b>3</b>), and isopimara-7,15-dien-3<i>β</i>-ol (<b>4</b>), in which <b>2</b> and <b>3</b> are identified as new derivatives. <i>In vitro</i> assays were conducted to evaluate the cytotoxic activity of compounds <b>1</b>-<b>4</b> against a panel of cancer cell lines and to determine the possible mechanism(s) related to the activity of the compounds on B16F10Nex2 cells. The most active compound <b>1</b> induced cytotoxic effects on tumor cells, with IC<sub>50</sub> values of 18.3, 52.1, and 58.9 µM against HL-60, HeLa, and B16F10-Nex2 tumor cells, respectively. Furthermore, it was observed in melanoma cells that compound <b>1</b> induced several specific apoptotic hallmarks, such as morphological changes in the cell shape structure, nuclear DNA condensation, specific chromatin fragmentation, and disruption in the mitochondrial membrane potential, which are related to the intrinsic apoptotic pathway.

Item Type: Article
Uncontrolled Keywords: Cell Line, Tumor, Hela Cells, HL-60 Cells, Animals, Humans, Mice, Meliaceae, Plant Leaves, Melanoma, Experimental, Terpenes, DNA, Neoplasm, Plant Extracts, Antineoplastic Agents, Phytogenic, Drug Screening Assays, Antitumor, Apoptosis, Molecular Structure, Brazil, Membrane Potential, Mitochondrial
Depositing User: Symplectic Admin
Date Deposited: 10 May 2018 13:57
Last Modified: 08 Jul 2022 12:10
DOI: 10.1055/s-0043-107241
URI: https://livrepository.liverpool.ac.uk/id/eprint/3021154