Leaf and Root Extracts from Campomanesia adamantium (Myrtaceae) Promote Apoptotic Death of Leukemic Cells via Activation of Intracellular Calcium and Caspase-3

Leaf and Root Extracts from Campomanesia adamantium (Myrtaceae) Promote Apoptotic Death of Leukemic Cells via Activation of Intracellular Calcium and Caspase-3

Author Campos, Jaqueline F. Google Scholar
de Toledo Espindola, Priscilla P. Google Scholar
Torquato, Heron F. V. Autor UNIFESP Google Scholar
Vital, Wagner D. Google Scholar
Justo, Giselle Z. Autor UNIFESP Google Scholar
Silva, Denise B. Google Scholar
Carollo, Carlos A. Google Scholar
Souza, Kely de Picoli Google Scholar
Paredes-Gamero, Edgar J. Autor UNIFESP Google Scholar
dos Santos, Edson L. Google Scholar
Abstract Phytochemical studies are seeking new alternatives to prevent or treat cancer, including different types of leukemias. Campomanesia adamantium, commonly known as guavira or guabiroba, exhibits pharmacological properties including antioxidant, antimicrobial, and antiproliferative activities. Considering the anticancer potential of this plant species, the aim of this study was to evaluate the antileukemic activity and the chemical composition of aqueous extracts from the leaves (AECL) and roots (AECR) of C. adamantium and their possible mechanisms of action. The extracts were analyzed by LC-DAD-MS, and their constituents were identified based on the UV, MS, and MS/MS data. The AECL and AECR showed different chemical compositions, which were identified as main compounds glycosylated flavonols from AECL and ellagic acid and their derivatives from AECR. The cytotoxicity promoted by these extracts were evaluated using human peripheral blood mononuclear cells and Jurkat leukemic cell line. The cell death profile was evaluated using annexin-V-FITC and propidium iodide labeling. Changes in the mitochondrial membrane potential, the activity of caspases, and intracellular calcium levels were assessed. The cell cycle profile was evaluated using propidium iodide. Both extracts caused concentration-dependent cytotoxicity only in Jurkat cells via late apoptosis. This activity was associated with loss of the mitochondrial membrane potential, activation of caspases-9 and -3, changes in intracellular calcium levels, and cell cycle arrest in S-phase. Therefore, the antileukemic activity of the AECL and AECR is mediated by mitochondrial dysfunction and intracellular messengers, which activate the intrinsic apoptotic pathway. Hence, aqueous extracts of the leaves and roots of C. adamantium show therapeutic potential for use in the prevention and treatment of diseases associated the proliferation of tumor cell.
Keywords natural products
medicinal plant
LC-MS
cancer
bioprospecting
Language English
Sponsor Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Mato Grosso do Sul (FUNDECT)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Instituto Nacional de Pesquisa do Pantanal - INPP
Fundação de Amparo e Desenvolvimento da Pesquisa Fadesp
Date 2017
Published in Frontiers In Pharmacology. Lausanne, v. 8, p. -, 2017.
ISSN 1663-9812 (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Origin http://dx.doi.org/10.3389/fphar.2017.00466
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000408514900001
URI http://repositorio.unifesp.br/handle/11600/51393

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