Abstract
The Australian whelk, Dicathais orbita, is a novel source of bioactive compounds with anticancer properties. Crude extracts from this mollusk have been found to have anticancer activity against a range of cell lines in vitro and were also effective at inducing apoptosis in vivo in a short-term rodent model for colorectal cancer. However, one important limitation of the preclinical model was toxicity in the liver due to lack of purification in the extract. Consequently, the aim of this research was to purify the bioactive compounds tyrindoleninone, tyrindolenine and the oxidation product 6-bromoisatin from the crude extract of D.orbita using flash column chromatography. The retention times and mass spectrum of the isolated compounds were obtained by liquid chromatography-mass spectrometry. These compounds were then tested for anti-cancer activity using a short-term (2 weeks) in-vivo mouse model using azoxymethane injection. Distal colon epithelial proliferation and apoptosis were evaluated using immunohistochemical staining and hematoxylin staining. Liver toxicity was assessed using serum alanine aminotransferase (AST), aspartate aminotransferase (ALT) and alkaline phosphatase (ALP) levels. Histopathology evaluation of liver was also performed by staining with hematoxylin and eosin. The results showed that the purified compounds had a greater anticancer effect than the crude extract, as evidenced by a significantly higher apoptotic index in the distal colon without any toxicity on liver. In conclusion this study has provided further scientific evidence for establishing the usefulness for this mollusk extract as a new medicine for the treatment or prevention of colon cancer.
Citation Format: Babak Esmaeelian, Kirsten Benkendorff, Richard Le Leu, Catherine Abbott. The preclinical effects of purified mollusk extracts in a short-term mouse model for early-stage colon cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B107.
Note: This abstract was not presented at the conference.