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Type: Artigo de periódico
Title: Xylodiol from Xylopia langsdorfiana induces apoptosis in HL60 cells
Author: Castello-Branco, MVS
Tavares, JF
Silva, MS
Barbosa, JM
Anazetti, MC
Frungillo, L
Haun, M
Diniz, MFFM
Melo, PS
Abstract: An atisane diterpene was isolated from Xylopia langsdorfi ana St. Hilaire & Tulasne, Annonaceae, leaves, ent-atisane-7 alpha, 16 alpha-diol (xylodiol). Preliminary study showed that xylodiol was cytotoxic and induced differentiation on human leukemia cell lines. However, the molecular mechanisms of xylodiol-mediated cytotoxicity have not been fully defined. Thus, we investigated the anti-tumor effect of xylodiol in human leukemia HL60 cell line. Xylodiol induced apoptosis and necrosis. HL60 cells treated with xylodiol showed biochemical changes characteristic of apoptosis, including caspases-8, -9 and -3 activation and loss of mitochondrial transmembrane potential (Delta psi(m)). However, there was a condensation rather than swelling of mitochondria. Moreover, the formation of condensed mitochondria and the loss of Delta psi(m) occurred downstream of caspase activation. Cyclosporine A did not protect HL60 cells from the cytotoxic effects of xylodiol, suggesting that the loss of Delta psi(m) is a late event in xylodiol-induced apoptosis. Oxidative stress was involved in xylodiol-induced apoptosis. Thus, we conclude that activated caspases cleave cellular proteins resulting in mitochondrial damage leading to mitochondrial condensation, loss of Delta psi(m) and ROS release from the mitochondria. ROS can further induce and maintain a collapse of Delta psi(m) leading to cellular damage through oxidation of lipids and proteins resulting in apoptotic cell death.
Subject: apoptosis
mitochondrial transmembrane
Xylopia langsdorfiana
Country: Brasil
Editor: Soc Brasileira Farmacognosia
Citation: Revista Brasileira De Farmacognosia-brazilian Journal Of Pharmacognosy. Soc Brasileira Farmacognosia, v. 21, n. 6, n. 1035, n. 1042, 2011.
Rights: aberto
Identifier DOI: 10.1590/S0102-695X2011005000135
Date Issue: 2011
Appears in Collections:Unicamp - Artigos e Outros Documentos

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