"" Ralph W. Moss, Ph.D., Cancer Advisor

Wednesday, September 30, 2015


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.


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:


D. James Morré, PhD
The outstanding work of Prof. D. James Morré and Prof. Dorothy Morré of Purdue University, Indiana, has focused renewed attention on green tea. That is because green tea is one of the compounds that inhibits the ENOX2 protein. ENOX2, discovered by the Morrés, is an undesirable product of the X chromosome that enables immature cancer cells to increase in size in preparation for renewed cell division.

Dorothy Morré, PhD
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. (It can vary from 20:1 to 50:1 tea to pepper, depending on the sources.) This has the effect of blocking the dangerous ENOX2, which functions on the surface of cancer cells. ENOX2 also enables cells to exhibit uncontrolled growth and the ability to invade neighboring tissues. When cancer cells are blocked in an immature stage, they cannot divide and within 72 to 96 hours will self-destruct in a process called apoptosis (a form of 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 EGCg. There are 1,300 articles referencing both EGCg and cancer.

Large Amount of Research

This is an unusually large amount of research on a natural product. 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, it 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).

Conducting trials on Capsol-T with its mixed catechins, instead of just brewed green tea or concentrated EGCg, will probably yield better results, whereas trials that utilize green tea, without the adjunctive addition of mild red pepper, and without an understanding of what this combination has to do, might very well come up with equivocal results.


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.

Monday, January 30, 2012

FDA Approves First Drug for Advanced BCC Skin Cancer

Jan. 30--The Food and Drug Administration (FDA) today approved a drug for the treatment of advanced basal cell carcinoma (BCC). This is the first drug ever approved for this condition and so I think this is important news. The name of the drug is vismodegib (trade name Erivedge®). It is marketed by the international drug giant Roche and its American subsidiary, Genentech. Erivedge is classified as a "hedgehog inhibitor," a new class of drugs.

In a clinical trial at the Karamanos Cancer Center, Detroit, published last year, it shrank these advanced skin tumors in 19 out of 33 cases (57.6%). There was preliminary evidence of activity in medulloblastoma (i.e., a kind of brain cancer). Grade 3 and 4 (serious or severe) adverse effects were also common (affecting almost 37% of patients).

The FDA approval of Erivedge is based on results from ERIVANCE BCC (SHH4476g), an international, single-arm, multicenter, two-cohort, open-label, Phase II study that enrolled 104 patients with advanced BCC, including locally advanced BCC (71) and metastatic BCC (33).

This study showed that Erivedge shrank lesions (i.e., had an objective response rate) in 43 percent (27/63) of patients with locally advanced BCC and 30 percent of patients (or 10/33) with metastatic BCC, as assessed by independent review, the primary endpoint of the study. The median duration of response was 7.6 months.

The pill will come at a steep price: $7,500 per month or $75,000 for a typical 10-month course. It is currently approved for patients with early stage BCC who cannot be treated with surgery or radiation.

LoRusso PM, Rudin CM, Reddy JC, et al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin. Cancer Res. 2011;17(8):2502-2511.

Wednesday, June 8, 2011

Another Phone Consultee Speaks

As you may know, I do phone consultations for cancer patients almost every day. I was very pleased to receive this feed-back comment the other day:

"When one receives a diagnosis of metastatic cancer all of a sudden you are thrust crudely into a new world of questions, doubt, fear and loathing. Ralph Moss is a bright mind and steady hand in providing trusted information in a way that one can sort things out and decide a pathway whether it be traditional Western Medicine or a Homeopathic approach. He can help confirm or deny your logical thoughts and your gut level instincts relative to the eventual decisions you will need to make." --T.T.

If I can be of help to you please email anne@cancerdecisions.com to make an appointment.

Tuesday, May 3, 2011

An MD Consultee Speaks

I have been doing many phone consultations lately, which is one of the reasons I have been remiss in adding entries to this blog. Everyone of my consultations is important to me and we always ask for feedback. Yesterday I did a consultation with a medical doctor and his wife (also a medical doctor). I was happy to help in this couple's decision making process. So here the response of one busy doctor to our consultation:

"Fabulous phone consult. Lots of suggestions, names & phone numbers of specialists to contact specific to my problem. Well worth the time and cost." —B.W., May 2, 2011

Tuesday, March 29, 2011

A Phone Consultee Speaks

As you may know, each day I do phone consultations for cancer patients. Today I got this nice comment from S.R., one of my recent consultees. She wrote as follows:

"At one point, I was reading 5 books simultaneously, on nutrition alone. Then I found out about Mr. Ralph Moss and Cancer Decisions website and started getting acquainted with his work. I purchased a report on my kind of cancer, read it, and later scheduled a conversation with Mr. Moss. The whole experience was eye-opening for me. He saved me months, maybe years of doing my own research. And still, I would never been able to find out everything he has written about. Mr. Moss has amazing insight not only in alternative therapies but also in nutrition. I am truly grateful! Now, I can make an informed decision about my health and future. Thank you again!"

Thursday, March 3, 2011

Vegan contest

It's getting a lot easier to find vegetarian and vegan food in many parts of the country!

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