*3.5. Anti-Cancer Extracts, Toxicity & Nutraceutical Potential*

Organic extracts from *D. orbita* egg masses, hypobranchial glands and mucus secretion effectively inhibit the proliferation of a range of cancer cell lines [19,23,26,71,77]. Bioassay guided fractionation indicated that the brominated indoles tyrindoleninone and tyrindolinone, as well as 6-bromoisatin are primarily responsible for this activity. A crude chloroform extract containing these brominated indole derivatives has also been shown to stimulate the acute apoptotic response to DNA-damage in the distal colon of mice, thus preventing early stage tumor formation [78]. Unpublished studies from my laboratory on the crude extracts and purified indoles suggest that these have no negative impacts on human immune cell function [22]. The crude extracts are generally not toxic in rodents, but can cause mild idiosyncratic hepatotoxicity in some mice [87]. Nevertheless, some liver damage is common with most chemotherapeutics and *D. orbita* extracts remain of interest due to their selective induction of apoptosis in cancerous or DNA damaged cells [71,78]. Further studies currently underway in my laboratory indicate that purified fractions containing the main active factor 6-bromoisatin have no effect on liver enzymes or hepatocytes *in vivo* [81]. As muricids comprise a traditional component of African [88], European [89], Mediterranean [90] and Asian [91] diets, there is excellent potential for the development of *D. orbita* as a novel medicinal food, particularly for colorectal cancer prevention, due to apparent bioavailability in the gastrointestinal tract. The historical and ongoing consumption of muricid meat implies an absence of symptomatic toxicity, although thorough investigation of the specific bioactive extracts is still required.

The combination of compounds with a range of bioactivities in the extracts of *D. orbita* is of particular interest for nutraceutical development [40,92]. In addition to the anticancer and antibacterial properties, *D. orbita* extracts appear to have a biphasic effect on progesterone steroidogenesis [19]. Furthermore, indirubin and some indoles are known to have anti-inflammatory properties. 5-Bromoisatin has been patented as an analgesic with sedative properties that reduce bleeding time in mice [93], suggesting 6-bromoisatin in *D. orbita* extracts could also have similar properties. To date, crude extracts from *D. orbita* containing choline esters not have been specifically tested for bioactivity or toxicity, despite the known muscle relaxing activity of these compounds (Table 2b). However, it is logical to assume than a concentrated extract containing these choline esters would retain the associated biological activity. Choline esters have also been suggested to act as immunological adjuvants in combined chemotherapy [94]. An extract containing muscle-relaxing, analgesic properties, antibacterial and anticancer activity could be particularly useful as a nutracetical or medicinal food [40]. Further studies are required to obtain an optimal concentration and combination of compounds to minimize any clinical side effects.
