Persin - Exploring the secret pharmacological life of the humble avocado

An important message for the under-the-table pet feeders of the world: If you feed your animal friend a bunch of avocado, it may get very sick [1]. This is thanks to a toxin called persin, which is found in both the fruit and leaves of the avocado tree (Persea americana). Persin is an polyketide that is made via the same biochemical pathways that the avocado plant uses to make fatty acids. It closely resembles linoleic acid, an essential omega-6 fatty acid.

For some reason, persin is usually harmless to humans (though it may be responsible for some avocado allergies) but can seriously mess with all sorts of other animals including birds, mammals (other than us), and fish. Lactating rodents and livestock that eat avocado leaves often develop udder-related problems such as inflammation and wonky milk secretion [2]. Avocado consumption has also been linked to heart damage (necrosis of myocardial fibres) in several mammals. This sort of selective toxicity is actually fairly common among drugs. For example, penicillin is pretty darn safe for humans (provided you aren't allergic), but it kills off guinea pigs like you wouldn't believe. Keep this in mind the next time your little furry bundle of joy and frequent excretion gets an infection and requires antibiotics.

Persin is also capable of harming fungi and insects, particularly those species that infect/eat the avocado plant (e.g. Colletotrichum gloeosporioides, which also attacks citrus fruits and papayas). This may explain why the compound exists in the first place!

In keeping with its toxic nature, persin is capable of killing breast cancer cells (hooray!). Not only that, it can boost the effects of tamoxifen, a popular breast cancer drug [3]. This synergistic effect is thought to be in part due to persin messing with steroid hormone receptor signaling so as to make breast cancer cells more susceptible to the estrogen receptor modulatory effects of tamoxifen.

[1] Buoro IB, Nyamwange SB, Chai D, Munyua SM. (1994). Putative avocado toxicity in two dogs. Onderstepoort J Vet Res. 61(1):107-109.
[2] Oelrichs PB, Ng JC, Seawright AA, Ward A, Schäffeler L, MacLeod JK. (1995). Isolation and identification of a compound from avocado (Persea americana) leaves which causes necrosis of the acinar epithelium of the lactating mammary gland and the myocardium. Nat Toxins. 3(5):344-349.
[3] Roberts CG, Gurisik E, Biden TJ, Sutherland RL, Butt AJ. (2007). Synergistic cytotoxicity between tamoxifen and the plant toxin persin in human breast cancer cells is dependent on Bim expression and mediated by modulation of ceramide metabolism. Mol Cancer Ther. 6(10):2777-2785.

1 chemically inspired comments:

Alison Butt said...

Thanks Chris - very interesting. Although we think the basis of the synergistic interaction between tamoxifen and persin is actually due to modulation of ceramide levels rather than steroid hormone receptor mediated, as it occurs in both estrogen receptor positive and negative cells.