Actin cytoskeleton as a putative target of the neem limonoid Azadirachtin A

Limonoids isolated from the Indian neem tree (A-zadirachia indica) have been gaining global acceptance in agricultural applications Lind in contemporary medicine for their myriad but discrete properties. However, then- mode or action is still not very well understood. We have studied the mode of action of Azadirachtin A, the major limonoid of neem seed extracts, using Drosophila melanoyaster Lis the model system. Azadirachtin A induces Moderate-to-severe phenotypes in different tissues in a close-dependent manner. At the cellular level, Azadirachtin A induces depolymerization of Actin leading to arrest of cells Lind Subsequently apoptosis in a caspase-indepen dent manner. Azadirachtin A-induced phenotypes were rescued by the over-expression of Cyclin E in a tissue-dependent manner. Cyclin E, which caused global rescue of Azadirachtin A-induced phenotypes, also effected rearrangement of the actin filaments. These results Suggest that probably actin is a target of Azadirachtin A activity. (c) 2007 Elsevier Ltd. All rights reserved.