Xylodiol from Xylopia langsdorfiana induces apoptosis in HL60 cells

Revista Brasileira de Farmacognosia

Barbosa Filho, José Maria¹  Anazetti, Maristella C.¹  Melo Diniz, Margareth F. F.¹  Faculdades Integradas Metropolitanas de Campinas, Brazil¹  Silva, Marcelo S.¹  Castello-Branco, Marianna Vieira S.¹  Frungillo, Lucas¹  Melo, Patrícia S.¹  Universidade Federal da Paraíba, Brazil¹  Tavares, Josean F.¹  Universidade Estadual de Campinas, Brazil¹  Haun, Marcela¹ 

关键词: apoptosis;    caspases;    mitochondrial transmembrane potential;    Xylopia langsdorfiana;    xylodiol;   

DOI  :  10.1590/S0102-695X2011005000135

来源: Sociedade Brasileira de Farmacognosia

【 摘 要 】

An atisane diterpene was isolated from Xylopia langsdorfiana St. Hilaire & Tulasne, Annonaceae, leaves, ent-atisane-7α,16α-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 (∆ Ψm). However, there was a condensation rather than swelling of mitochondria. Moreover, the formation of condensed mitochondria and the loss of ∆ Ψm occurred downstream of caspase activation. Cyclosporine A did not protect HL60 cells from the cytotoxic effects of xylodiol, suggesting that the loss of ∆ Ψm 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 ∆ Ψm and ROS release from the mitochondria. ROS can further induce and maintain a collapse of ∆ Ψm leading to cellular damage through oxidation of lipids and proteins resulting in apoptotic cell death.

【 授权许可】

Unknown