Mar. Drugs 2014, 12(1), 17-35; doi:10.3390/md12010017
Article

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

1 School of Biological Sciences, Flinders University, GPO Box 2100, Adelaide 5001, Australia 2 Flinders Centre for Innovation in Cancer, Flinders University, GPO Box 2100, Adelaide 5001, Australia 3 Preventative Health National Research Flagship, CSIRO, PO Box 10041, Adelaide BC 5000, Australia 4 Marine Ecology Research Centre, School of Environment, Science and Engineering, Southern Cross University, GPO Box 157, Lismore, NSW 2480, Australia These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 30 October 2013; in revised form: 30 November 2013 / Accepted: 4 December 2013 / Published: 24 December 2013
(This article belongs to the Special Issue Marine Compounds and Cancer)
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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.
Keywords: apoptosis; azoxymethane; bioactive natural product; colorectal cancer; isatin; in vivo model; marine mollusc

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MDPI and ACS Style

Esmaeelian, B.; Abbott, C.A.; Le Leu, R.K.; Benkendorff, K. 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. Mar. Drugs 2014, 12, 17-35.

AMA Style

Esmaeelian B, Abbott CA, Le Leu RK, Benkendorff K. 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. 2014; 12(1):17-35.

Chicago/Turabian Style

Esmaeelian, Babak; Abbott, Catherine A.; Le Leu, Richard K.; Benkendorff, Kirsten. 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." Mar. Drugs 12, no. 1: 17-35.

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