A. Catassi A. Cesario D. Arzani P. Menichini A. Alama C. Bruzzo A. Imperatori N. Rotolo P. Granone P. Russo +39 0105600217 patrizia.russo@istge.it Translational Research B (Lung Cancer), Department of Integrated Medical Oncology (DOMI) National Cancer Research Institute Largo Rosanna Benzi 10 16132 Genoa Italy Center of Thoracic Surgery University of Insubria Varese Italy Department of Surgical Science, Division of General Thoracic Surgery Catholic University Rome Italy Clinical Respiratory and Pathology Translational Laboratory IRCCS San Raffaele Rome Italy Division of Hygiene Catholic University Rome Italy Department of Translational Oncology, Molecular Mutagenesis Unit National Cancer Research Institute Genoa Italy Abstract. The effects of different marine derived agents were studied in A549 cell growth. These drugs induced cell cycle arrest at the G 2 -M phase associated with the up-regulation of GADD45α − γ and down-regulation of c-Myc. In treated cells, GADD45α − γ and c-Myc were up- and down-regulated, respectively. A cascade of events leading to apoptotic mitochondrial ‘intrinsic’ pathway was observed in treated cells: (1) dephosphorylation of BAD serine 136 ; (2) BAD dissociation from 14-3-3 followed by its association with BCL-XL; (3) cytochrome c release; (4) caspase-3 activation, and (5) cleavage of vimentin. Caspase(s) inhibitor prevented the formation of cleavage products and, in turn, apoptosis was inhibited through a p53-independent mechanism. Moreover, these compounds did not activate NF-κB. Our findings may offer new insights into the mechanisms of action of these agents in A549 cells. The better understanding of their effects might be important to fully exploit the potential of these new drugs.
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Characterization of apoptosis induced by marine natural products in non small cell lung cancer A549 cells
A., Catassi; A., Cesario; D., Arzani; P., Menichini; A., Alama; C., Bruzzo; A., Imperatori; N., Rotolo; P., Granone; P., Russo
Follow Cellular and Molecular Life Sciences
, Volume 63 (19)
Springer Journals – Oct 1, 2006
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