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Human cancer cell (Jurkat) killing by the cyanobacterial metabolite calothrixin A

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Abstract

Calothrixin A is a bioactive metabolite of the cyanobacterium Calothrix and has been shown to be active at nanomolar concentrations against human HeLa cancer cells. It induces apoptotic killing of human Jurkat cancer cells in a time- and concentration-dependent manner, as revealed by flow cytometry, morphological evidence from electron microscopy and DNA fragmentation. It also causes G2/M cell cycle arrest, which is indicative of intracellular DNA damage. It was shown to be redox-active, as measured by oxygen uptake in the presence of dithiothreitol, and caused cleavage of plasmid DNA, as revealed by electrophoresis. This cleavage was blocked by the H2O2 scavenger catalase, but not by other scavengers of reactive oxygen species (ROS). Calothrixin A appeared to induce intracellular formation of ROS as measured by fluorescence of dichlorodihydrofluorescein diacetate. Conditions were not found, however, under which the calothrixin A-induced apoptosis could be reversed by the scavengers, or by the metal chelator desferal. Menadione was compared with calothrixin A. The IC50 at which this compound caused apoptosis was significantly higher. It also induced cell cycle arrest at higher concentrations, although caused plasmid DNA cleavage at lower concentrations. It is postulated that the greater effectiveness of calothrixin A in killing cells is related to its ring structure, which has the characteristics of a DNA intercalator, thereby localizing its quinone-dependent effects.

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Authors and Affiliations

  1. School of Biochemistry and Molecular Biology, The Australian National University, ACT, 0200, Australia

    Xinxin Chen & Geoffrey D. Smith

  2. Department of Chemistry, Faculty of Science, The Australian National University, ACT, 0200, Australia

    Paul Waring

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  1. Xinxin Chen
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  2. Geoffrey D. Smith
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  3. Paul Waring
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Chen, X., Smith, G.D. & Waring, P. Human cancer cell (Jurkat) killing by the cyanobacterial metabolite calothrixin A. Journal of Applied Phycology 15, 269–277 (2003). https://doi.org/10.1023/A:1025134106985

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  • DOI: https://doi.org/10.1023/A:1025134106985

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