Researchers report that a purple compound produced by the Australian white rock sea snail to protect its eggs has also shown potential as a new anticancer pharmaceutical. The team from Flinders University, Southern Cross University, and Monash University in Australia isolated the compound in the gland secretions from Dicathasis orbita which has antibacterial, anti-inflammatory and anticancer properties. The scientists published their study (“Mapping insoluble indole metabolites in the gastrointestinal environment of a murine colorectal cancer model using desorption/ionization on porous silicon imaging”) in Scientific Reports.
“Indole derivatives are a structurally diverse group of compounds found in food, toxins, medicines, and produced by commensal microbiota. On contact with acidic stomach conditions, indoles undergo condensation to generate metabolites that vary in solubility, activity, and toxicity as they move through the gut. Here, using halogenated ions, we map promising chemo-preventative indoles, i) 6-bromoisatin (6Br), ii) the mixed indole natural extract (NE) 6Br is found in, and iii) the highly insoluble metabolites formed in vivo using desorption/ionization on porous silicon-mass spectrometry imaging (DIOS-MSI). The functionalized porous silicon architecture allowed insoluble metabolites to be detected that would otherwise evade most analytical platforms, providing direct evidence for identifying the therapeutic component, 6Br, from the mixed indole NE,” the investigators wrote.
“As a therapeutic lead, 0.025 mg/g 6Br acts as a chemo-preventative compound in a 12-week genotoxic mouse model; at this dose 6Br significantly reduces epithelial cell proliferation, tumor precursors (aberrant crypt foci; ACF), and tumor numbers while having minimal effects on liver, blood biochemistry, and weight parameters compared to controls. The same could not be said for the NE where 6Br originates, which significantly increased liver damage markers. DIOS-MSI revealed a large range of previously unknown insoluble metabolites that could contribute to reduced efficacy and increased toxicity.”
“After a decade of work, we have found an active compound derived from the substance produced by the mollusc’s gland which could be used as a preventative in bowel cancer,” said senior lead scientist Catherine Abbott, PhD, from Flinders University. “We’re very excited about these latest results and hope to attract investment from a pharma company to work on a new drug to reduce development of colorectal cancer tumors.”
Using mass spectrometry technology, the research team has been able to pinpoint the lead active compound which, in the future, could be put to good work, she added. Colorectal cancer is the second leading cause of the 9.6 million cancer deaths every year, with the World Health Organization reporting 862,000 deaths in 2018.
Natural compounds from marine and terrestrial plants and animals are valuable sources of current and future medicines for human health, said Southern Cross University marine scientist Kirsten Benkendorff, PhD, who is also researching the potential of replicating the snail species’ anti-inflammatory compound.
“In this latest research we have not only shown that a specific snail compound can prevent the formation of tumors in a colon cancer model, but we were also able to use sophisticated technology to trace the metabolism of the compound inside the body,” explained Benkendorff. “This is very important for drug development because it helps demonstrate the absence of potentially toxic side-effects.”
Along with tracking the active compound inside the body to confirm it reaches the colon where it has the anti-tumor effect, which is important for oral drug delivery, the snail compound comes from indoles, which are commonly found in both natural plant medicines and some pharmaceuticals.
“We were able to use the fact that snail compound contains bromine like a unique fingerprint to trace how these types of compounds are metabolized inside the body and identify some potentially toxic metabolites from the crude extracts that were not found with the pure snail compound,” Benkendorff added. “This research is very important for understanding the safety of these types of natural compounds for human medicine.”
