"" Ralph Moss—Cancer Consultant: 2015-09-27

Wednesday, September 30, 2015

NEW INTEREST IN GRAVIOLA

Graviola, also known as soursop

One surprising finding in James and Dorothy Morrés' groundbreaking book, ECTO-NOX Proteins: Growth, Cancer and Aging, is that a class of compounds known as Acetogenins are also ENOX2- inhibitors. ENOX2 is a protein found on the surface of almost all cancer cells. Acetogenins, in turn, are ingredients or byproducts of a plant family known scientifically as Annonaceae. These are mainly tropical plants found mainly in the rain forests of South America and Southeast Asia. The best-known of these is graviola, also known as soursop. There are over 130 of these Acetogenin compounds (Mangal 2015). Scientists consider Annonaceae to be "chemically one of the least investigated family" of plants (ibid.). But they deserve greater attention and are now being investigated as possible anticancer agents.

Graviola (Annona muricata) is a well-known folk remedy for cancer, with a devoted following in some countries. It is used as a pesticide, antimalarial, antiparasitic and antimicrobial and now as an anticancer agent (Fang 1993). But these compounds also have some general cytotoxicity, which is related to their ability to interfere with the energy use by cells (Ahammadsahib 1993). This is what may make this herb toxic to normal cells under some conditions and has brought it to the attention of various writers, not all of whom are sympathetic to its use.

As the Morrés state in their book, "a more selective activity is necessary to explain the ability of certain acetogenins to kill cancer cells under conditions where normal cells are unharmed." This is where ENOX2 comes in. Twenty years ago, Morré and his Purdue colleague, Jerry L. McLaughlin, PhD, carried out an experiment with one particular acetogenin, bullatacin. This is a fatty acid compound found in some Annonaceae fruit. They showed that bullatacin almost completely inhibited ENOX2 activity in HeLa cancer cells (Morré 1995). Scientists in Atlanta, Georgia, recently showed that whole-plant extracts of graviola leaf are indeed toxic to cancer cells. However, they caution that this extract, “despite its superior in vitro and in vivo efficacy, resulted in death of the mice due to toxicity” (Yang 2015).

This raises the question of whether graviola is too toxic to use, and, if it is used, how great is the risk to cancer patients? A particular concern is the presence of a neurotoxin, annonacin, in the leaves.

Alexander Schauss, PhD, a well-respected scholar in the field of natural products, has spoken out forcefully against the general use of graviola in food supplements. He says that there is an association between graviola consumption and "atypical" Parkinson’s disease. He did research on this topic a dozen years ago in Guam, where the consumption of graviola is common. A 2006 report from Guadaloupe similarly made a connection between graviola and Parkinsonism. It stated that Parkinsonism on this Caribbean island was "associated with the consumption of plants of the Annonaceae family, especially Annona muricata...suggesting a possible toxic etiology…Consumption of Annonaceae may contribute to the pathogenesis of atypical parkinsonism in Guadeloupe" (Lannuzel 2006). These are chilling words.

For that reason, I would say that cancer patients should stay away from graviola, until further research shows that it is both effective at inhibiting ENOX2 in humans and that there is a safe level of consumption that will not cause or contribute to Parkinson's disease. 

Pawpaw Tree

Another question is whether a related North American plant, pawpaw (Asimina triloba) might be a safe substitute for graviola. Otherwise known as the "Indiana banana," this tree produces a surprisingly delicious tropical-tasting fruit, even in the Eastern parts of the United States. (I recently recovered one from a tree growing on a local university campus: it was surprisingly delicious.) The topic of pawpaw and cancer deserves an article of its own. But the aforementioned Dr. Jerry McLaughlin has written that pawpaw contains "promising new antitumor...agents that are found only in the plant family Annonaceae" (Alali 1998). So there is promise in pawpaw.


References

Ahammadsahib KI, Hollingworth RM, McGovren JP, Hui YH, McLaughlin JL. Mode of action of bullatacin: a potent antitumor and pesticidal annonaceous acetogenin. Life Sci. 1993;53(14):1113-1120.

Alali FQ, Liu XX, McLaughlin JL. Annonaceous acetogenins: recent progress. J Nat Prod. 1999;62(3):504-540. doi:10.1021/np980406d.

Lannuzel A, Höglinger GU, Champy P, Michel PP, Hirsch EC, Ruberg M. Is atypical parkinsonism in the Caribbean caused by the consumption of Annonacae? J Neural Transm Suppl. 2006;(70):153-157.

Morré DJ and Morré D. ECTO-NOX PROTEINS: GROWTH, CANCER AND AGING. New York: Springer, 2013. (List price of $267 but available from the Harvey H. and Donna M. Morré Foundation for Cancer Research, 1112 Cherry Lane, West Lafayette, IN 47906 by enclosing a check for a donation of $100 made out to the Foundation and also by providing a mailing address.)

Yang C, Gundala SR, Mukkavilli R, Vangala S, Reid MD, Aneja R. Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer. Carcinogenesis. 2015;36(6):656-665. doi:10.1093/carcin/bgv046.

Alexander Schauss, PhD, interview: