"" Ralph Moss—Cancer Consultant: 2015

Tuesday, December 1, 2015


Sam Donato, New Jersey mushroom hunter
(Photo © 2015 M. B. Moss)

Recently, I was on a site visit to the ProCure Proton Beam Therapy center in Somerset, NJ, when I took time out for a walk in that town’s magnificent Colonial Park. On one of the rambling paths through the woods my wife and I almost literally bumped into a local man. We got to talking and he identified himself as Sam Donato. He was now a published author and musician, but for most of his life had made his living as a truck driver and construction worker.

 My wife admired and commented on his corncob pipe. It turned out that not only his pipe, but his tobacco was homemade, in the latter case, grown and cured in central New Jersey! Sam informed us that he was out hunting for mushrooms, and one in particular, the “hen of the woods.” You can usually find them, he told us, growing at the base of oak trees between September and November.

I know “hen of the woods” well. Otherwise known as maitake (Grifola frondosa or Grifola umbellata, it is a mushroom of importance in complementary and alternative medicine (CAM). Like many mushrooms, it has both immune-stimulating and anti-cancer properties. It is also said to help control high blood pressure. Sam was unaware of these medicinal uses, but simply enjoyed the delicious taste of them.

We eventually went our separate ways, but about half an hour later, our trails looped around and we encountered him once again crossing our path. He informed us that he had found a large maitake at the base of an oak tree. He took us to his car and revealed this ten pound fungus, which he was about to take home and sautée in butter. It was indeed a hen of the woods. My wife took this photo of him in the parking lot of Colonial Park, the proud discoverer of one of this elusive but famous mushroom.

The word “maitake” means “dancing mushroom” in Japanese. This is because ordinary Japanese people would dance for joy whenever they found one, since the Emperor offered its weight in silver for anyone who found one. Nowadays, you can buy extracts as a food supplement (such as Grifola’s Maitake D fraction) or even sometimes find fresh ones in the supermarket.

There is a considerable amount of research on maitake mushrooms—285 PubMed-indexed articles. Of these, 82 concern cancer. The most recent comes from Kobe University—for historical and cultural reasons, most of the research on maitake originates in Japan. It is generally conceded that maitake is an “immune stimulant.” But what exactly does this mean? The Kobe scientists showed that the soluble beta-glucan-rich “D fraction” of maitake “acts as a potent immunotherapeutic agent” and specifically that (together with another immune stimulant) iincreased dendritic cell activity against cancer, “resulting in tumor regression via an antitumor T helper cell 1-type response.”

“Our findings provide the basis for a potent antitumor therapy using a novel combination of immunologic agents for future clinical immunotherapy studies in patients,” Yuki Masuda and colleagues wrote. This confirms what has been known for decades—that mushrooms such as maitake, shiitake, Trametes versicolor, etc. contain immune modulating compounds. Now that immunotherapy is popular in oncology, one would expect increased attention paid to these time-honored and virtually non-toxic methods of boosting immunity.


Dr. James M. Arnott of Brighton, England

Have you heard about the "new" treatment for cancer called cryotherapy? This is the use of extreme cold to destroy tumors, and hopefully cure the disease. I put the word "new” in quotes because cryotherapy is actually an old treatment. A mid-nineteenth century surgeon named James Arnott (1797-1883) began using "cryo" in Brighton, England in 1845 and even published a book on the subject six years later (Arnott 1851). Arnott exhibited his apparatus at the Great Exhibition in London—the famous Crystal Palace Exhibition of 1851. 

The famous Crystal Palace, home of the 1851 Great Exhibition in London, England

Arnott's work would thus have been accessible to tens of thousands of visitors, including such famous Britons as Prince Albert, Charles Dickens and Charles Darwin. James Arnott was assisted in his work by his older brother, Neil Arnott, FRS, of Baker Street, who (among many other things) invented the waterbed.

That’s right—“cryo” was already well-known and practiced ten years before the American Civil War! For cancer, Arnott used salt solutions containing crushed ice to attain temperatures of -18º to -24º C (i.e., - 0.4º to – 11º F). He used this apparatus to freeze advanced cancers of the breast and cervix. This resulted in a decrease in the size of the tumor, a reduction of drainage and an amelioration of pain (Gage 1998).

At the time, Arnott wrote these prophetic words:

“Congelation [freezing, ed.] arresting the accompanying inflammation, and destroying the vitality of the cancer cell, is not only calculated to prolong life for a great period, but may, not improbably, in the early stage of the disease, exert a curative action.”

Arnott was certainly ahead of his time. Freezing a tumor seems intrinsically safer than removing it by surgery. What then happened to cryotherapy? Why wasn’t it instantly and universally adopted as a superior method of destroying tumors. First of all, Arnott’s apparatus was bulky and cumbersome. Second, a tumor had to be essentially external in character to be successfully treated in the era before asepsis and anaesthesia. Finally, the temperatures that were attained by the Arnott apparatus were probably not cold enough to thoroughly destroy the tissues in question. A historian of this question has stated:

“Though the usefulness of cold application was acknowledged by Arnott’s contemporaries and physicians of the time began to use local freezing techniques, further development of cryosurgery had to await advances in technology, especially the development of better cryogenic agents.”

The use of cryotherapy to treat cancer of the prostate gland only began in earnest in the 1960s (Wilson 1966). Drs. Ward A. Soanes and Maurice J. Gonder of Kenmore, NY, are credited with developing modern apparatus for the trans-urethral freezing of the prostate gland. In 1966, these two Upstate urologists told the American Urological Association (AUA) that they had treated 150 patients with "no mortality and minimal morbidity” (JAMA 1966). It was the beginning of a new era in prostate cancer treatment, although progress has been undeniably slow over the past few decades.

Cryotherapy continues to be an option for many cases of prostate cancer and other malignancies and is offered at dozens of medical centers around the US and the world. To find an oncologist or urologist who uses this technique one can conveniently consult the Web site of the Endocare company:


Arnott J. On the treatment of cancer by the regulated application of an anesthetic temperature. London: J. Churchill, 1851.

 JAMA. Cryosurgery on prostate reported. JAMA. 1966;196(13):29-29. doi:10.1001/jama.1966.03100260019007.

Gage AA. History of cryosurgery. Semin Surg Oncol. 1998;14(2):99-109. doi:10.1002/(SICI)1098-2388(199803)14:2<99::AID-SSU2>3.0.CO;2-1.

Wilson CB, Winternitz WW, Bertan V, Sizemore G: Stereotaxic cryosurgery of the pituitary gland in carcinoma of the breast and other disorders. JAMA 1966; 198:587–S90.

Saturday, October 31, 2015


Parsley and other herbs contain apigenin (from Wikimedia Commons)

In 1936, Albert Szent-Györgyi, MD, PhD, whose biography I wrote (Free Radical), discovered a class of bioactive compounds that controlled hemorrhaging in certain medical conditions (Armentano 1936). These compounds are found in many plants, including his native Hungarian paprika and lemon juice. Fresh from his isolation of ascorbic acid, or vitamin C, he named these new compounds, collectively, “vitamin P.” However, since no known diseases were associated with a lack of this “vitamin,” the name was eventually changed to bioflavonoids, or simply flavones. The word “flavone” comes from the Latin word for “yellow,” the dominant color of these pigment-like compounds. In recent years, attention has focused on one particular flavone called apigenin.

There are now over 3,000 PubMed-indexed journal articles discussing apigenin, with a new one appearing about every day. Over 600 articles relate to its role in cancer. A fascinating example appeared in September 2015. The first author was Sanjeev Shukla, PhD, in a research group headed by Prof. Sanjay Gupta of Case Western Reserve University, Cleveland. These Ohio scientists found that apigenin effectively inhibited a molecule called IKKα. IKKα is an enzyme complex involved in regulating a transcription factor called NF-kappaB, responsible for cellular response to inflammation (Häcker 2006). They describe IKKα as a "key driver of the metastatic process" and therefore a "promising therapeutic target in anticancer drug research." Their key point is as follows:

"Suppression of IKKα kinase activation…by apigenin might markedly reduce cancer progression…” (Shukla 2015).
Until recently, no potent inhibitor of IKKα had been identified. But these Case Western scientists have now identified an effective inhibitor of this undesirable enzyme—apigenin. Apigenin, they wrote, "exhibits anticancer efficacy in experimental tumor model." It does this by directly binding to IKKα and suppressing genes associated with the invasiveness and migration ability of human prostate cancer cells. In mice, apigenin stops tumor growth, lowers the proliferation rate of malignant cells and enhances apoptosis (the predominant form of programmed cell death). They identified some other anticancer effects. Apigenin:
  • Causes cell cycle arrest in prostate cancer cells.
  • Suppresses migration in cancer cells.
  • Suppresses tumor growth in athymic nude mice.
There may be some special relationship between apigenin and prostate cancer:
“Accumulated evidence leads us to hypothesize that there is some distinct mechanism by which apigenin suppresses prostate cancer growth, and we believe this warrants further investigation.”
This 2015 article is not alone in identifying apigenin as a potent anticancer agent. A small but interesting clinical trial was performed in Groß-Gerau, Germany, and was published by Prof. Harald Hoensch of the University of Frankfurt. His group gave a food supplement of 10 milligrams (mg) of apigenin as well as 10 mg of EGCg (a main ingredient in green tea) to patients who had either colorectal cancer or premalignant polyps of the colon. The results were dramatic. In the control group, 47 percent (7 out of 15) had recurrences either of cancer or of their polyps. But in the treated group, only 7 percent (1 out of 14) had a recurrence. Writing in the World Journal of Gastroenterology. Hoensch said:
“Sustained long-term treatment with a flavonoid mixture could reduce the recurrence rate of colon neoplasia [cancer, ed.] in patients with resected colon cancer" (Hoensch 2008).
By now, I am sure that many readers will be wondering where they can get this amazing apigenin. It is actually quite readily available in the food supply. The most abundant sources are dried parsley leaves and grapefruit. According to one nutritional Web site (merschat.com), dried parsley has an incredible 13,000 mg per 100 grams. In other words, it is 13 percent apigenin by weight! Fresh parsley has a considerable 225 to 300 mg per 100 grams. Other good sources are peppermint, thyme, raw celery and rutabagas. There is also apigenin in chamomile flower tea.

Put another way, one cup of chopped raw parsley has over 180 mg of apigenin. To get a 10 mg dose, as in the clinical trial, you would only need to take one tablespoon of raw chopped parsley per day. Alternately, you could sprinkle a small amount of dried parsley into your food. One can buy dried organic parsley in bulk. The Frontier herb coop offers a one-pound bag of certified organic parsley leaf flakes for $25 dollars on Amazon. If you consumed one gram per day (the equivalent of two supplement capsules), this bag would last you well over a year. This works out to around 5¢ per day. This is of course best done as part of a comprehensive, holistic life-style modification program.

It seems unlikely that readers could harm themselves by taking this food factor. The toxicity of apigenin consists of an occasional allergic reaction, or possibly an undesirable interactions with other drugs. There is, however, one laboratory study that seemed to show that although apigenin was effective at killing leukemia cells, it simultaneously interfered with one standard drug used in the chemotherapy of that same disease (Ruella-de-Sousa 2010). It thus might be wise to NOT take high doses of this chemical if you are currently undergoing chemotherapy for cancer. At the very least you should discuss this with your oncologist. Most reasonable doctors would not object to you adding a tablespoon of parsley to your daily regimen. It could do a world of good.

Acknowledgement: My thanks to Prof. Sanja Gupta of Case Western Reserve University, Cleveland, for reading and commenting on this article. Any remaining errors are the author's responsibility.


Armentano PL, Bentsath A, Beres T, et al. Über ein Einfluss von Substanzen der Flavongruppe...Deutsche Med Wochschr. 1936;62:1326–1328.

Häcker H, Karin M. Regulation and function of IKK and IKK-related kinases". Sci. STKE 2006 (357): re13. doi:10.1126/stke.3572006re13. PMID 17047224.

Hoensch H, Groh B, Edler L, Kirch W. Prospective cohort comparison of flavonoid treatment in patients with resected colorectal cancer to prevent recurrence. World J Gastroenterol. 2008;14(14):2187-2193.

Ruela-de-Sousa RR, Fuhler GM, Blom N, Ferreira CV, Aoyama H, Peppelenbosch MP. Cytotoxicity of apigenin on leukemia cell lines: implications for prevention and therapy. Cell Death and Dis. 2010;1(1):e19. doi:10.1038/cddis.2009.18.

Schreiber A, Carle R, Reinhard E. On the accumulation of apigenin in chamomile flowers. Planta Med. 1990;56(2):179-181. doi:10.1055/s-2006-960920.

Big Advances in Prostate Cancer

3 Tesla MRIs are revolutionizing detection of prostate cancer

There have been considerable advances in the past few years in both the detection and treatment of prostate cancer. Typically, in the past, patients were screened for prostate cancer using the prostate specific antigen (PSA) test. If the test score was over 4 the man was considered a likely candidate for a prostate biopsy. This biopsy was and is guided by a transrectal ultrasound (TRUS) device. The urologist would take a certain number of “punch” biopsy samples of the prostate gland. This might turn up a malignant area, which was then classified according to the Gleason scale (from a low of 2 to a high of 10).
However, ultrasound typically is not a very precise way of visualizing tumors or distinguishing them from non-malignant areas. Nowadays, much more precise magnetic resonance imaging (MRI) is increasingly being used as a superior way of visualizing the prostate and isolating abnormalities including, possibly, cancer. The modern so-called "3 Tesla" MRI machine has twice the strength of the older 1.5 Tesla MRIs and about 10 to 15 times the strength of low-field or open MRI scanners. It produces remarkably clear images, far ahead of what has been generally available to one's urologists, especially those in more outlying areas. These images can be further enhanced by the insertion of an endorectal coil, which serves as a kind of antenna for the MRI machine. These 3 Tesla MRIs are already in operation at some of the leading medical centers, but even there the patient may need to insist on being screened with a “3T” machine as opposed to the older but more readily available "1.5T" machines. To find centers with 3T machines may require repeated and intense phoning.

While most people who receive an MRI of the prostate have already had a TRUS-guided biopsy, this is not necessarily the case. Some doctors are now willing to prescribe a 3T MRI as the first line for evaluation after detecting a lump via a digital rectal exam (DRE) or through an elevated PSA or other test.

Fusion Technology

A positive finding on the MRI will probably result in a decision to do a biopsy. Typically, this is an outpatient procedure in which a urologist inserts a hollow needle between12 to 24 times into the gland in a search for cancerous tissue. The gland is usually treated with a local anesthetic before the procedure, but still is fairly unpleasant. Older biopsies were to some degree a hit or miss affair. But prostate biopsies nowadays can be performed using a so-called “fusion” system. UroNav is one such system. It provides a way of combining traditional trans-rectal ultrasound with an MRI image to produce a clear picture of which areas need to be sampled for malignancy. In the words of Eric A. Klein, MD, of the Cleveland Clinic, with the typical random biopsy "we're using a scattershot 'blind' approach, hoping that, if a tumor is present, one of the needles will encounter it. These random biopsies can miss some harmful tumors, while turning up others that are inconsequential and may end up being treated unnecessarily." The UroNav system was introduced at a urology meeting in 2013 and quickly became available at many top centers, including Brigham and Women’s and Beth Israel Deaconess, Boston; Cleveland Clinic, Cleveland; New York University (NYU) Langone Medical Center, New York; the National Cancer Institute, Bethesda; Yale Medical Center, New Haven, etc.

Once a patient has undergone this fusion biopsy, there is a good chance that he will have a definitive answer of whether or not he has cancer and if so, how malignant and dangerous it is likely to be. However, the treatment picture remains complex. For instance, lower malignancy tumors (typically, a Gleason score of six or less or low-volume Gleason 7 tumors (i.e., a Gleason pattern of 3+4) can usually be managed through active surveillance (what used to be called watchful waiting). This might involve periodic repeat biopsies. At some centers, such as NYU Langone, there is a comprehensive program of integrative oncology, under the direction of Geo Espinosa, ND, to prolong this period of active surveillance (hopefully) or co-management of more advanced prostate cancer for the duration of the patient’s life. On the other hand, tumors with high volume and a Gleason score of 7, 8 or higher usually require immediate treatment. Treatment decisions need to be individualized, based on many considerations, including the patient’s age, general fitness, and of course desires. This “fine tuning” should be done under the guidance of a knowledgeable urologist/oncologist.

What prostate cancer treatment is best remains a matter of dispute. In the past, radical prostatectomy (RP) was virtually the only option. Then came radiation therapy, both external beam, intensity modulated radiation therapy (IMRT) and/or radioactive seeds (brachytherapy). These still remain valid options for many people. More recently, there has been increasing interest in non-ionizing forms of energy, such as radiofrequency ablation (RFA), high intensity frequency ultrasound (HIFU) and cryo-ablation (freezing the tumor and the prostate gland). As stated, for those with lower malignancy tumors an aggressive program of life-style modification, including dietary changes, might be sufficient. In this sense, urology is moving faster than some other specialties towards a state of integrative oncology.

In any case, while prostate cancer remains an enormous problem in the US and elsewhere, diagnostic and treatment options have expanded in recent years in a direction favorable to the potential patient.

Acknowledgement: My thanks to Dr. Geo Espinosa, ND, of NYU Langone Medical Center, for reading and commenting on this article. Any remaining errors are the author's responsibility.

Friday, October 23, 2015

ECTO-NOX Proteins: Growth, Cancer and Aging (Book Review)


© 2015 by Ralph W. Moss, PhD

Once in a rare while a scientific book comes along that, while highly technical in nature, also contains information of urgent importance to patients and their caregivers. Such a book is ECTO-NOX Proteins: Growth, Cancer and Aging (Springer 2013). This astonishing book offers a detailed and well-organized record of five decades of research by the husband-and-wife team of D. James Morré, PhD and Dorothy Morré, PhD, mainly conducted as professors at Purdue University in West Lafayette, Indiana. James Morré, the Dow Professor of Medicinal Chemistry, was the founding director of Purdue’s cancer research center.

In this groundbreaking book, the Morrés explain the global significance of a class of proteins called “ECTO-NOX,” which is commonly abbreviated ENOX. The “ECTO” prefix means that these various proteins, regardless of where their originating genes reside, are ultimately expressed on the surface or exterior of cells (from the ancient Greek ectos, “outside”). There are presently three known classes of ENOX proteins. ENOX1 is a normal constituent of most cells. ENOX2 is found in cancer of many kinds. ENOX3, also called arNOX, is an age-related class of proteins. These various ENOX proteins are crucially involved in cell growth, biological time keeping, cancer, aging and even viral infections. They also share some similarities to prions, which are proteins that are responsible for a number of human illnesses (such as “mad cow disease”). 

James Morré, PhD
These proteins are unique in a number of ways. For instance, their expression depends on a particular biological clock, or circadian rhythm, that (depending on the form of ENOX) varies from 22 to 26 minutes. They alternately carry out two separate physiological functions in rapid succession. The explanation in this book of these peculiarities is very clear and will strike most readers with a background in science as revolutionary in its implications for basic biology.

Particularly thought provoking are the Morrés’ discussions of ENOX2 and ENOX3. ENOX2 is specific for cancer and plays an indispensable role by allowing an immature cancer cell to enlarge to a normal size. The Morrés spent decades perfecting a practical test for ENOX 2, which is now called ONCOblot. This test can reputedly differentiate among 26 different types of cancer. According to oncoblotlabs.com, the test can detect tumors as small as 1 mm in diameter, which represents about 2 million cells. This makes it about ten times more sensitive than a typical Positron Emission Tomography (PET) scan. If cancers can be detected at this early stage, and differentiated as to tissue of origin, then this alone represents a huge advance in the cancer field. It would allow for the possibility of early detection and then medical intervention to eliminate small tumors before they become increasingly difficult to treat. 

Dorothy Morré, PhD

James Morré told me that he and his wife refused to release the ONCOblot test to the public until they had discovered a way to convert an elevated test score back to normal, presumably by curing very early stage cancers (personal communication, July 2015). 
The practical upshot of this is a pill called Capsol-T. This is a 25:1 mixture of decaffeinated green tea powder and a low-heat guajillo red pepper. The red pepper potentiates the activity of the green tea ten- to one hundred-fold. In a clinical trial involving 110 subjects, 40 percent of them tested positive for ENOX2 on ONCOblot. They then took Capsol-T for around four months. They took it around the clock, every four hours (using a sustained release form before bedtime). The result was that 94 percent no longer showed as positive for ENOX2 on a repeat test. They were presumably cured of early-stage, non-clinical cancer.

Green tea is no stranger to the world of medical research. There are presently ~2,000 articles on the topic in PubMed, 1,337 of which involve the main catechin, EGCg. But while Capsol-T might sound like just another empirical cancer remedy, its use is based upon a prolonged and intensive scientific study, based around its ability to inhibit ENOX2. There was nothing haphazard about the way these food constituents were put together. It turns out to be the most effective natural inhibitor of ENOX2 in cancer cells. Its own activity is enhanced between 10 and 100 times by the concurrent administration of a small amount of red pepper. In fact, in the laboratory this combination is almost as effective as the powerful (and toxic) chemotherapy drug, Adriamycin, at inhibiting ENOX2. 

I hope the reader now senses the enormous potential of this line of research, the fruit of more than 50 years of determined work at Purdue and elsewhere. (James Morré himself has published 399 PubMed-indexed scientific papers.) If we now truly have a way to detect very early cancers, differentiate their tissue of origin, and then treat and eliminate them in their preclinical stages, I believe that the Morrés have gone a long way to solving the cancer puzzle! This proposition of course requires further testing. But, at this point, the burden of proof shifts from these individuals to the large and well-funded government and private agencies, which have the capacity to carry out large-scale tests. The fact that they have not done so is both puzzling and frustrating. One hopes this is not another instance of the determined suppression of a generic and non-toxic approach in the interest of entrenched medical interests.


The Morrés’ discussion of aging will be revelatory for those who are concerned about the ravages of time on the human organism. The Morrés also identified a substance called ENOX3, also called the age-related ENOX (abbreviated arNOX), which is similar in its fundamental structure to ENOX2, although it originates from genes on different chromosomes. ENOX3 begins to appears at around age 30, and then increases into one’s 60s or 70s. The amount of ENOX3 in blood or saliva correlates quite strongly with one’s apparent age. In other words, the more ENOX3 one has, the older one looks. 

In the laboratory, the Morrés have discovered that certain readily available, non-toxic substances strongly inhibit the destructive effects of ENOX3, thus suppressing one of the mainsprings of the aging process. Key among these is coenzyme Q10. CoQ10 is made in the human body but is also widely available as a food supplement. 

Another surprising fact in this book is that certain herbs are protective against ENOX3. These are especially the famous French mixture, the herbs de Provence. This a mixture of dried herbs that are typical of the Provence region of southeast France. But the Morrés discovered that the most effective and beneficial of these herbs is summer savory (Satureja hortensis). These herbs are very active in human biology, even at the minute levels used in French cooking. I presently use both the dried and fresh forms of these herbs and intend to keep cultivating them, especially savory, indoors throughout the winter months.

In sum, since 1960, the scientists James and Dorothy Morré have produced an amazing body of scientific work, which they have summarized with admirable clarity in this 500-page text. The book contains more than 1,000 scientific references, many of them by the Morrés, their students and coworkers at Purdue University, as well as a very useful and detailed index. Hats off also to the publisher, Springer, since I could not find a single typographical error in the entire book (a rare publishing achievement these days). 

Some of the explanations in ECTO-NOX Proteins are by necessity very detailed and specialized and so non-specialist readers may find themselves skipping over some  technical discussions. But the general thrust of the argument is not hard to follow. Once you understand what is at stake in this line of research, you will read this book as the great scientific detective story that it is. If you have an intense interest in questions of growth, cancer or aging, or want to learn more about the anti-cancer and anti-aging potential of ENOX protein inhibitors, you definitely will not want to miss this groundbreaking book.
NOTE: My only caveat about this book is the price, which is $267 on Amazon ($219 on Kindle). However, readers of this article can obtain a hardcover copy of ECTO-NOX Proteins 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 to the foundation and providing a mailing address.

For the Morrés cancer test and treatment:

Oncoblot test: http://oncoblotlabs.com/

Capsol-T treatment: http://www.capsol-t.com/

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: