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

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

Author Conserva, Geanne Alexandra A. Autor UNIFESP Google Scholar
Girola, Natalia Autor UNIFESP Google Scholar
Figueiredo, Carlos R. Autor UNIFESP Google Scholar
Azevedo, Ricardo A. Google Scholar
Mousdell, Sasha Google Scholar
Sartorelli, Patricia Autor UNIFESP Google Scholar
Soares, Marisi G. Google Scholar
Antar, Guilherme M. Google Scholar
Lago, Joao Henrique G. Google Scholar
Abstract Guarea macrophylla 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 G. macrophylla using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of four compounds: cycloart-23E-ene-3 beta,25-diol (1), (23S*,24S*)-dihydroxycicloart-25-en-3-one (2), isopimara-7,15-diene-2 alpha,3 beta-diol (3), and isopimara-7,15-dien-3 beta-ol (4), in which 2 and 3 are identified as new derivatives. In vitro assays were conducted to evaluate the cytotoxic activity of compounds 1-4 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 1 induced cytotoxic effects on tumor cells, with IC50 values of 18.3, 52.1, and 58.9 mu M against HL-60, HeLa, and B16F10-Nex2 tumor cells, respectively. Furthermore, it was observed in melanoma cells that compound 1 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.
Keywords Guarea macrophylla
Meliaceae
cycloartane triterpene
isopimarane diterpene
cytotoxicity
cancer cells
apoptosis
xmlui.dri2xhtml.METS-1.0.item-coverage Stuttgart
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
CNPq
Grant number FAPESP: 2014/08961-2
FAPESP: 2015/11936-5
Date 2017
Published in Planta Medica. Stuttgart, v. 83, n. 16, p. 1289-1296, 2017.
ISSN 0032-0943 (Sherpa/Romeo, impact factor)
Publisher Georg Thieme Verlag Kg
Extent 1289-1296
Origin http://dx.doi.org/10.1055/s-0043-107241
Access rights Closed access
Type Article
Web of Science ID WOS:000415714600005
URI https://repositorio.unifesp.br/handle/11600/58263

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