"" Ralph Moss—Cancer Consultant: 2015-10-25

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.