Cytotoxic effect of Laxaphycins A and B on human lymphoblastic cells (CCRF-CEM) using digitised videomicrofluorometry

In Vivo. 2005 May-Jun;19(3):577-82.

Abstract

Laxaphycin A (laxa A) and Laxaphycin B (laxa B), cyclic peptides isolated from the terrestrial blue-green alga Anabaena laxa or the marine cyanobacterium Lyngbya majuscula have antifungal and cytotoxic activities. We used numerical videomicrofluorometry and a protocol of multiple labelling with Hoescht 33342 (nuclear DNA), Rhodamine 123 (mitochondria) and Nile Red (plasma membrane) to study the cytotoxicity of these substances in human lymphoblastic cells sensitive (CEM-WT) or resistant (CEM-VLB and CEM-VM1) to anticancer agents. The results indicate a low resistance index of 2 for CEM-VLB cells treated with laxa B or laxa A + lava B. For the three cell strains, following laxa B treatment, we observed an increase of a polyploid cell subpopulation that could result from the alteration of topoisomerase-II activity. On the contrary, the simultaneous treatment by laxa A and laxa B led to a decrease of that subpopulation with increasing laxa A doses. However, the effect of laxa A was less pronounced in the CEM-VM1 cells, which present a low intrinsic topoisomerase-II activity. For CEM-VLB cells, the higher doses needed can be attributed to their MDR resistance. Though we observed a synergistic effect between laxa B and laxa A (the latter is inactive by itself), these results indicate a different mode of action for laxa B and laxa A + laxa B. A more precise study of the mode of action of these compounds is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyanobacteria
  • Drug Resistance, Neoplasm
  • Fluorometry
  • Humans
  • Leukemia, Lymphoid / pathology*
  • Microscopy, Video
  • Peptides, Cyclic / toxicity*

Substances

  • Laxaphycin A
  • Laxaphycin B
  • Peptides, Cyclic