The aromatic head group of spider toxin polyamines influences toxicity to cancer cells

Wilson, David, Boyle, Glen M., McIntyre, Lachlan, Nolan, Matthew J., Parsons, Peter G., Smith, Jennifer J., Tribolet, Leon, Loukas, Alex, Liddell, Michael J., Rash, Lachlan D., and Daly, Norelle L. (2017) The aromatic head group of spider toxin polyamines influences toxicity to cancer cells. Toxins, 9 (11). 9110346. pp. 1-13.

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Abstract

Spider venoms constitute incredibly diverse libraries of compounds, many of which are involved in prey capture and defence. Polyamines are often prevalent in the venom and target ionotropic glutamate receptors. Here we show that a novel spider polyamine, PA366, containing a hydroxyphenyl-based structure is present in the venom of several species of tarantula, and has selective toxicity against MCF-7 breast cancer cells. By contrast, a polyamine from an Australian funnel-web spider venom, which contains an identical polyamine tail to PA366 but an indole-based head-group, is only cytotoxic at high concentrations. Our results suggest that the ring structure plays a role in the cytotoxicity and that modification to the polyamine head group might lead to more potent and selective compounds with potential as novel cancer treatments.

Item ID: 52888
Item Type: Article (Research - C1)
ISSN: 2072-6651
Keywords: spider venom; NMR spectroscopy; polyamine; cancer; cytotoxicity
Additional Information:

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Funders: Breast Cancer Foundation, National Health and Medical Research Council of Australia (NHMRC), Australian Research Council (ARC)
Projects and Grants: NHMRC 1020114, ARC FF110100226
Date Deposited: 28 Mar 2018 01:43
FoR Codes: 06 BIOLOGICAL SCIENCES > 0602 Ecology > 060203 Ecological Physiology @ 100%
SEO Codes: 96 ENVIRONMENT > 9605 Ecosystem Assessment and Management > 960506 Ecosystem Assessment and Management of Fresh, Ground and Surface Water Environments @ 100%
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