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Naturally occurring asteriscunolide A induces apoptosis and activation of mitogen‐activated protein kinase pathway in human tumor cell lines by Gledy Negrín; José L. Eiroa; Manuel Morales; Jorge Triana; José Quintana; Francisco Estévez is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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Sesquiterpene lactones have attracted much attention because they display a wide range of biological activities, including antitumor properties. Here, we show the effects of the naturally occurring sesquiterpene lactone asteriscunolide A (AS) on viability of human melanoma, leukemia and cells that overexpress antiapoptotic proteins, namely Bcl-2 and Bcl-x(L). All cell lines were sensitive to this compound, with IC(50) values of approximately 5 microM. The cytotoxic effects of AS were accompanied by a G(2)-M phase arrest of the cell cycle and a concentration- and time-dependent appearance of apoptosis as determined by DNA fragmentation, translocation of phosphatidylserine to the cell surface and sub-G(1) ratio. Apoptosis was associated with caspase-3 activity and poly(ADP-ribose) polymerase cleavage and was prevented by the nonspecific caspase inhibitor z-VAD-fmk, indicating that caspases are essential components in this pathway. The apoptotic effect of AS was also associated with (i) the release of cytochrome c from mitochondria which was accompanied by dissipation of the mitochondrial membrane potential (Delta Psi(m)) and (ii) the activation of the mitogen-activated protein kinase

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Author

Gledy Negrín; José L. Eiroa; Manuel Morales; Jorge Triana; José Quintana; Francisco Estévez

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0899-1987)

Published

2010

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)