Side Effects

From quirky to serious, trends in psychology and psychiatry

Fighting Cancer with Science and Nature

Why natural agents that kill cancer cells warrant further investigation.

In the U.S. (and across the West, more generally), we are understandably suspicious of medical hoaxes and scams, given the damage they can cause. Our media and pundits try to weed out medical assertions that are unsupported by science. The Internet, in particular, abounds with dubious products whose untested, often wildly oversold effects can easily persuade the unthinking and the credulous to part with their cash.

Yet as someone who follows and comments on developments in especially psychiatry, I frequently am struck by the faith we place in products that come with FDA approval, but a litany of unpleasant, sometimes risky side effects. When, for example, millions of men across America are willing to "double their risk of hearing loss" and jeopardize their eyesight for an erection, as recent studies warn about those routinely taking Viagra, you know that potency is something we take very seriously. Enough to tune out such warnings and opt unthinkingly for a blue pill, rather than a wealth of natural aphrodisiacs whose effect is basically identical—minus, of course, the nasty health risks.

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When our knowledge of natural products is also limited, even impoverished, by cultural biases that skew toward pharmaceuticals, our information-base shrinks accordingly. We ignore the well-known medicinal properties of vast amounts of natural products and end up placing enormous faith in pills whose very advertisements are forced to devote significant amounts of time and space to a laundry list of side effects. (The U.S. shares with New Zealand the dubious distinction of being the only Western countries to allow direct-to-consumer advertising of psychotropic pharmaceuticals.)

Because I also spend large amounts of time in South America, in particular Peru, from where I'm blogging this summer, cultural differences in medicine and public health can be especially striking. From here, over the last few weeks, I've been able to follow with intense interest the arguments both for and against naturally existing cancer-fighting agents, such as the leaves of the guanabana tree (hereafter known as "graviola"). From all that I've been able to investigate, from PubMed to the National Cancer Institute at the National Institutes of Health, my sense is that the leaves of this remarkably promising fruit should be getting more rather than less attention from the scientific community. As the studies below indicate, there is already strong evidence that acetogenins in the plant’s leaves target tumors in what scientists call “apoptosis,” or programmed cell death. Unlike in chemotherapy, however, that targeting, according to Zeng et al (1996b), is “relatively nontoxic to noncancerous cells.” In Peru, graviola is routinely part of a cancer-fighting arsenal, along with chemotherapy. In the States the latter prevails, eclipsing most other options.

First, some key background. About three years ago, word spread rapidly on the web about the cancer-fighting properties of "graviola," the leaves of the guanabana tree (Annona muricata), also known as "soursop," "cherimoya," "custard apple," and "Brazilian paw paw." The tree grows in Peru, Colombia, and Brazil, as well as countries in sub-Saharan Africa and South-East Asia with similarly temperate climates. In all of these countries, the fruit is eaten widely; it is often put in shakes and fruit salads, because it is so delicious. Additionally, the leaves and fruit are frequently used to treat viruses, infections, and depression. There is also, apparently, limited production of the fruit in southern Florida.

As millions of people suffer from all kinds of cancers, for which we have treatments such as radiation and chemotherapy (generally, with terrible side effects) but no cure, interest in and demand for graviola, in particular, skyrocketed around 2008 when reports of its efficacy started to rise. At the same time, some small businesses and a few hucksters, generally selling graviola with a host of other products (essiac tea, burdock root, sheep sorrel, blue-green algae, and so on), overstated their medicinal effects, whose accuracy had also been exaggerated in all the hubbub and excitement. Very quickly, a treatment known to kill some cancer cells and tumors (see below) morphed inaccurately into assurance about cancer's cure.

As rapidly as excitement had skyrocketed, skeptics rushed to denounce the "cancer cure" as a fraud and scam afflicting the needy, the desperate, and the gullible. The Federal Trade Commission (FTC) swooped in to fine and close various businesses that had unwisely reported an ability to cure cancer. And in September 2008, Medical News Today publicized the FTC's actions, quoting its director of the Bureau of Consumer Protection, Lydia Parkes, as saying: "There is no credible scientific evidence that any of the products marketed by these companies can prevent, cure, or treat cancer of any kind" (my emphases).

The only problem with Parkes's blanket dismissal of all these elements is that, in the case of graviola at least, her claim wasn't in fact true.

In 1976, as Richard D. McCarthy, MD, reports on the encyclopedic cancer website U.S. Cancer Centers: Cancer Center Information and Research, "The NCI or the National Cancer Institute did some research on the guanabana cancer cure [sic] and came up with some interesting results. The study . . . showed that the leaves and stems of the plant were incredibly efficient at destroying certain cancerous cells in the body."

"Inexplicably," another site notes, "the results [of the NCI research] were published in an internal report and never released to the public. Since 1976, guanabana has proven to be an immensely potent cancer killer in 20 independent laboratory tests, but as of now, no double-blind clinical trials. [However], a study published in the Journal of Natural Products, following a recent study conducted at Catholic University of South Korea, stated that one chemical in guanabana was found to selectively kill colon cancer cells at '10,000 times the potency of (the commonly used chemotherapy drug) Adriamycin. '... The most significant part of the Catholic University of South Korea report is that guanabana was shown to selectively target the cancer cells, leaving healthy cells untouched."

Adds the same site, "A study at Purdue University, Indiana, recently found that leaves from the guanabana tree killed cancer cells among six human cell lines and were especially effective against prostate, pancreatic and lung cancers." The article, "Paw Paw and Cancer: Annonaceous Acetogenins from Discovery to Commercial Products," appearing in Journal of Natural Products 71.7 in 2008, was authored by Dr. Jerry L. McLaughlin of Purdue's Department of Medicinal Chemistry and Molecular Pharmacology. The journal is published by the American Chemical Society and American Society of Pharmacognosy.

In response to the predictably enormous rise in public interest in graviola, Cancer Research UK also released a statement about the alleged cancer "cure" that included these sentences:

"In laboratory studies, graviola extracts can kill some types of liver and breast cancer cells that are resistant to particular chemotherapy drugs. But there haven't been any large-scale studies in humans. So we don't know yet whether it can work as a cancer treatment or not. Overall, there is no evidence to show that graviola works as a cure for cancer."

On the basis of the laboratory studies quoted here, with Cancer Research UK acknowledging that "graviola extracts can kill some types of liver and breast cancer cells," you might think that such preliminary but hopeful results would at least warrant further investigation. As the site states, "we don't know yet," implying a desire for further research, but also essentially acknowledging ignorance because of the rather astonishing absence of "large-scale studies in humans."

What's startling about the reaction in the United States, by contrast, was that the FTC's action overrode the initial findings of the National Cancer Institute. Even more puzzling, the NCI, after establishing those findings, decided against publicizing them and, for reasons unclear to me, against pursuing them further.

Here in Peru, by contrast, the leaves of the guanabana tree—in short, the very parts of it that both the NCI and CR determined do in fact have cancer-fighting properties—are widely considered part of a parallel set of treatments against cancer, along with chemotherapy and the removal of tumors through operations. In the case of one woman I interviewed, the former mayor of a small town (Supe) three hours north of Lima, graviola was noted by her doctor both for helping to kill cancer cells and for greatly boosting the immune system, itself a common victim of chemo, which destroys more than just cancer cells. In both cases, science supports his recommendation.

After an operation to remove a cancerous tumor in one of her ovaries, the woman (whose information I am relaying with her permission) was given a combined treatment of chemotherapy and a dietary supplement of graviola, taken with meals three times a day. (It's taken either in capsule form or as a tea with boiling water; in either case, that should always be in consultation with a doctor or oncologist). One year later, after she had battled intense side effects from chemo—including hairloss, skin damage, and nausea—she wasn't just in remission. Her cancer had completely disappeared. It remains gone to this day, two years later.

Although it is impossible in this case to distinguish clearly where the effects of chemo ended and those of graviola began, a carefully administered large-scale human trial could control for that variable. My point, then, is not to state or even imply that graviola is a "cure" for cancer. Following the science, I am instead urging that the States and other countries fund and advance such research, owing precisely to the initial findings of the National Cancer Institute and, more recently, of Purdue's Cancer Center.

In Peru, to point up the differences and give readers more information, a major chain, Bionaturista, with stores across the capital and surrounding country, grinds the guanabana leaves into powder under laboratory conditions, with all equipment carefully sterilized, and exports it to a client-base around the world. The chain is one of Peru's largest exporters—not bad for a country whose enviable economic boom is owing partly to its vast natural reserves of minerals and natural gas.

Nor, I should add, is graviola alone among natural products in having anticancer properties. In 2006, to cite Wikipedia, "a research team from the Ben Gurion University in Israel found that lemongrass (Cymbopogon citratus) also caused apoptosis (programmed cell death) in cancer cells." A key ingredient in especially Thai and Vietnamese cuisine, lemongrass—which is widely and inexpensively available across South-East Asia, South America, and in certain Western stores and supermarkets—is also routinely used as a delicious, healthful tea. According to the published studies below, its potency in killing cancer cells is dwarfed by that of graviola.

In urging that a lot more funding and research go into investigating why graviola kills certain kinds of malignant cancer cells, apparently I risk the ire of the FTC's Bureau of Consumer Protection. But rather than give a blanket dismissal of graviola and guanabana, perhaps the FTC should heed the findings of both the NCI and Cancer Research UK and look into this further. The health of millions of cancer sufferers and survivors around the world quite clearly depends on it.

www.christopherlane.org Follow me at @christophlane

Further References:

Chang, F.R., and Y.C. Wu, "Novel Cytotoxic Annonaceous Acetogenins from Annona muricata." J. Nat. Prod. 64.7 (2001): 925-931: http://www.ncbi.nlm.nih.gov/pubmed/11473425

McLaughlin, J.L., "Paw Paw and Cancer: Annonaceous Acetogenins from Discovery to Commercial Products." J. Nat. Prod. 71.7 (2008): 1311-21: http://www.ncbi.nlm.nih.gov/pubmed/18598079  : “The extract (in capsule form) enhances a mixture of natural anthelmintics. In addition, an encapsulated extract has been effectively used by certain cancer patients as a botanical supplement product.”

Oberliesa, N. H., J. L. Jonesb, T. H. Corbettb, S. S. Fotopoulosc, and J. L. McLaughlin, "Tumor cell growth inhibition by several Annonaceous acetogenins in an in vitro disk diffusion assay," Cancer Letters 96:1 (September 4, 1995), 55-62: http://www.ncbi.nlm.nih.gov/pubmed/7553608: "The cell inhibition activities of several Annonaceous acetogenins, covering the three major structural classes of bis-adjacent, bis-non-adjacent, and single tetrahydrofuran (THF) ring compounds and their respective ketolactone rearrangement products, were tested in an in vitro disk diffusion assay against three murine (P388, PO3, and M17/Adr) and two human (H8 and H125) cancerous cell lines as well as a non-cancerous immortalized rat GI epithelial cell line (I18). The results demonstrate a dose-dependent inhibition of cancerous cell growth, while non-cancerous cell growth is not inhibited by the same dosages. All of the acetogenins, irrespective of their various structural types, inhibit the growth of adriamycin resistant tumor cells and non-resistant tumor cells at the same levels of potency. These results show that the Annonaceous acetogenins are an extremely potent class of compounds, and their inhibition of cell growth can be selective for cancerous cells and also effective for drug resistant cancer cells, while exhibiting only minimal toxicity to 'normal' non-cancerous cells" (my emphases).

Pomper, K.W., Lowe, J.D., Crabtree, S.B., and Keller W. “Identification of annonaceous acetogenins in the ripe fruit of the North American pawpaw (Asimina triloba ).” J. Agric Food Chem. 2009 Sep 23; 57(18):8339-43: http://www.ncbi.nlm.nih.gov/pubmed/19711911: “This plant contains annonaceous acetogenins in the twigs, unripe fruit, seeds, roots, and bark tissues, which display antitumor, pesticidal, antimalarial, anthelmintic, piscicidal, antiviral, and antimicrobial effects, suggesting many potentially useful applications.”

Rupprecht J.K., Hui Y.H., McLaughlin J.L. “Annonaceous acetogenins: A Review.” J. Nat Prod. 53.2 (1990):237-78: http://www.ncbi.nlm.nih.gov/pubmed/2199608

Zeng, L., Q. Ye, N.H. Oberlies, G. Shi, Z-M. Gu, K. He, and J.L. McGaughlin, "Recent Advances in Annonaceous Acetogenins." NPR: Natural Product Reports 13.4 (1996): 275-306: http://www.ncbi.nlm.nih.gov/pubmed/8760865

Zeng, L., F.-E. Wu, N.H. Oberlies, J.L. McLaughlin, and S. Sastrodihadjo, "Five New Monotetrahydrofuran Ring Acetogenins from the Leaves of Annona muricata," J. Nat. Prod. 59.11 (1996): 1035–1042: http://www.ncbi.nlm.nih.gov/pubmed/8946744: "The high potencies of the Annonaceous acetogenins in various bioassay systems have been demonstrated experimentally to be due to their inhibition of ATP production through both the inhibition of the NADH-ubiquinone oxidoreductase (Complex I) of mitochondrial electron transport systems and the ubiquinone-linked NADH oxidase in the plasma membranes of tumor cells. These combined actions may be linked to programmed cell death (apoptosis). The acetogenins are effective against drug resistant cell lines, and they are relatively nontoxic to noncancerous cells" (my emphasis).

Christopher Lane, Ph.D., teaches literature and intellectual history at Northwestern University and is the author of Shyness: How Normal Behavior Became a Sickness. more...

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