Characterization of apoptosis induced by marine natural products in non small cell lung cancer A549 cells

Cell Mol Life Sci. 2006 Oct;63(19-20):2377-86. doi: 10.1007/s00018-006-6264-7.

Abstract

The effects of different marine derived agents were studied in A549 cell growth. These drugs induced cell cycle arrest at the G2-M phase associated with the up-regulation of GADD45alpha-gamma and down-regulation of c-Myc. In treated cells, GADD45alpha-gamma 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 serine136; (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-kappaB. 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.

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Lung Neoplasms / pathology
  • Marine Toxins / pharmacology*
  • Mitochondria / metabolism
  • NF-kappa B / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Vimentin / metabolism
  • bcl-Associated Death Protein / metabolism
  • bcl-X Protein / metabolism

Substances

  • 14-3-3 Proteins
  • Antineoplastic Agents
  • BAD protein, human
  • BCL2L1 protein, human
  • Cell Cycle Proteins
  • GADD45A protein, human
  • MYC protein, human
  • Marine Toxins
  • NF-kappa B
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Vimentin
  • bcl-Associated Death Protein
  • bcl-X Protein
  • Cytochromes c