A NEW LOOK AT GRAVIOLA FOR CANCER TREATMENT

Published by Ralph W. Moss, Ph.D., Cancer Advisor – Sept. 30, 2015
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.

Twenty years ago, Morré and his Purdue colleague, Jerry L. McLaughlin, PhD, carried out an experiment with one particular acetogenin, bullatacin, a fatty acid compound found in some Annonaceae fruit. They showed that it almost completely inhibited ENOX2 activity in HeLa cancer cells (Morré 1995).graviola no

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.

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. This tree produces a surprisingly delicious tropical-tasting fruit, even in the Eastern parts of the United States.

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.

MORE CLINICAL TRIALS FOR GREEN TEA?

D. James Morré, PhD
Dorothy Morré, Ph

Green tea is not the only thing that can inhibit ENOX2. There are several well-known anticancer agents that do so, including two jack-of-all-trade drugs, cisplatin and doxorubicin (better known by its trade name, Adriamycin®). Almost as powerful, and far less toxic, is a specific combination of concentrated green tea and pure chili pepper, which is sold as “Capsol-T.”

It combines these two ingredients in a particular ratio, which is determined experimentally for each product lot. This has the effect of blocking the dangerous ENOX2, which functions on the surface of cancer cells.

 “A major factor in the effectiveness of Capsol-T is the necessity to take the product every four hours even during the night. The effect of Capsol-T on ENOX2 is one of reversible inhibition….The effect of both green tea and Capsol-T is transient and goes away in a matter of a few hours. If cancer cells can be prevented from growing for more than three or four days they are likely to undergo programmed cell death.”

 There are currently ~6,000 scientific publications indexed in PubMed on the topic of green tea. Over ~2,000 of these contain references to the main medicinal substance found in tea, the polyphenol (or catechin) dubbed epigallocatechin gallate or EG

Cg. There are 1,300 articles referencing both EGCg and cancer.

 Large Amount of Research

Complementary and alternative medicine (CAM) subjects are usually deficient in solid research and, often, scientific research lags behind popular interest. But you can see that green tea is among the best researched subjects in the nutritional universe.

Unfortunately, the clinical investigation of green tea in human cancer patients has lagged behind the easier-to-perform laboratory studies. However, in the April 2015 issue of the journal Prostate,there was a very interesting article on the effects of brewed green tea compared to brewed black tea (and plain water) on various blood markers associated with prostate cancer development and progression.

Dr. Suzanne M. Henning and colleagues at the David Geffen School of Medicine, University of California, Los Angeles, CA (UCLA) conducted the study. In this phase II trial, 113 men who had been diagnosed with prostate cancer were randomized to consume six cups daily of brewed green tea, brewed black tea or water prior to undergoing a radical prostatectomy (RP) operation. The authors looked at a variety of markers of progression. Patients who consumed green tea (but not either black tea or water) had a significant decrease in the amount of nuclear factor kappa B [NFκB]. NFκB is a very important marker that is often associated with more aggressive cancers.

In fact, tea polyphenols (including EGCg) were detected in the prostate tissue of 32 of the 34 men who received green tea, but not in the two other groups. Evidence of a systemic antioxidant effect was  observed only with green tea consumption. Also, only green tea led to a statistically significant decrease in serum prostate-specific antigen (PSA) levels.

The authors concluded “future longer-term studies are warranted to further examine the role of GT [green tea, ed.] for prostate cancer prevention and treatment, and possibly for other prostate conditions such as prostatitis.”

In September, this conclusion was seconded by a well known urologist at New York University’s Langone Medical Center, New York, Samir S. Taneja, MD. Writing in the Journal of Urology(official journal of the American Urological Association), Taneja wrote:

 “The authors of this [UCLA, ed.] study provide a well executed trial with defined, measurable end points. While the study does not tell us if green tea will prevent prostate cancer or slow its growth, it offers insight into potential mechanisms and validates a biological effect of the agents, such that future clinical trials of efficacy appear warranted” (Taneja 2015).

Such a trial will probably be less significant if the green tea in question is given solely as a brewed drink than in the form proposed by the Morrés, namely as Capsol-T. The reason for this has to do with the presence of ENOX2 at the surface of most cancer cells (including prostate cancer cells) and the ability of various substances, including green tea catechins, to inhibit in turn the functions of ENOX2.

 It is important to note that Capsol-T must be taken according to a rigorous schedule.

Dr. Morré recently told me:

“A major factor in the effectiveness of Capsol-T is the necessity to take the product every four hours even during the night. The effect of Capsol-T on ENOX2 is one of reversible inhibition….The effect of both green tea and Capsol-T is transient and goes away in a matter of a few hours. If cancer cells can be prevented from growing for more than three or four days they are likely to undergo programmed cell death.

However, if the Capsol-T or green tea levels are intermittent, the cancer cells will resume growth when the levels reach a low blood level and the clock starts over again and will never be killed and through a ‘survival of the fittest’ selection process may even become resistant. This is why, to be effective, Capsol-T must be taken every 4 hours, even during the night” (personal communication, September 21, 2015).

For a better understanding, interested readers can and should read the Morrés’ articles (e.g., Hanau 2014) and, especially, their groundbreaking book, ECTO-NOX Proteins: Growth, Cancer, and Aging (Springer 2013).

 References:

Hanau C, Morré DJ, Morré DM. Cancer prevention trial of a synergistic mixture of green tea concentrate plus Capsicum (CAPSOL-T) in a random population of subjects ages 40-84. Clin Proteomics. 2014;11(1):2. doi:10.1186/1559-0275-11-2.

Henning SM, Wang P, Said JW, et al. Randomized clinical trial of brewed green and black tea in men with prostate cancer prior to prostatectomy. Prostate. 2015;75(5):550-559. doi:10.1002/pros.22943.

Mangal M, Khan MI, Agarwal SM. Acetogenins as potential anticancer agents. Anticancer Agents Med Chem. June 2015.

Morré DJ, de Cabo R, Farley C, Oberlies NH, McLaughlin JL. Mode of action of bullatacin, a potent antitumor acetogenin: inhibition of NADH oxidase activity of HeLa and HL-60, but not liver, plasma membranes. Life Sci. 1995;56(5):343-348.

Taneja SS. Re: Randomized Clinical Trial of Brewed Green and Black Tea in Men with Prostate Cancer Prior to Prostatectomy. J Urol. 2015;194(3):704-705. doi:10.1016/j.juro.2015.06.050.

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.

 

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