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6-bromoisatin found in muricid mollusc extracts inhibits colon cancer cell proliferation and induces apoptosis, preventing early stage tumor formation in a colorectal cancer rodent model
Marine Drugs
  • Babak Esmaeelian, Flinders University
  • Catherine A Abbott, Flinders University
  • Richard K Le Leu, Flinders University
  • Kirsten Benkendorff, Southern Cross University
Document Type
Article
Publication Date
1-1-2014
Peer Reviewed
Peer-Reviewed
Abstract
Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC50 223 μM (0.05 mg/mL) and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g) was found to significantly enhance the apoptotic index (p ≤ 0.001) and reduced cell proliferation (p ≤ 0.01) in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer.
Citation Information

Esmaeelian, B, Abbott, CA, Le Leu, RK & Benkendorff, K 2014, '6-bromoisatin found in muricid mollusc extracts inhibits colon cancer cell proliferation and induces apoptosis, preventing early stage tumor formation in a colorectal cancer rodent model', Marine Drugs, vol. 12, no. 1, pp. 17-35.

Article available on Open Access