Thanks to Anne Caputi** for the following information: 8/03 UPDATE: Recently numbers of visitors to this site have been writing to me inquiring about the powerful rainforest herb, Graviola. I would like to clarify my experience and recommendations regarding this herb. I have never used Graviola as a single bulk herb. I use a very high quality liquid herbal tincture which is a combination of Graviola and numbers of other rainforest herbs. This combination of herbs is specifically designed to enhance and potentiate the power of Graviola. Graviola has been shown to have an effect on cancer cells which can be of great benefit to someone who is fighting cancer. Because it is so effective, it is important to supplement the use of graviola with herbs which support detoxification and protection of the major detoxyfing organs. I use Gravizon, a comprehensive formula produced by The Amazon Herb Company. The main ingredient in Gravizon is graviola Graviola is a medium size shrub growing in the Amazonian jungle. The graviola tree produces a delicious fruit commonly called paw-paw, which is widely consumed by indigenous people. Nearly 25 years ago it was discovered that the leaf of the graviola tree contained natural compounds having exceptional cytotoxic activity. In other words, they had a very strong ability to prevent abnormal cellular division. In that sense, Gravizon is considered a unique product for immune support, assisting the immune system in cleaning abnormal tissue growth. When the immune system works in this manner to "clean up" tissues, it must be able to easily reach the target tissue and the debris must be eliminated effectively. For this reason, in Gravizon, graviola is blended with Recovazon (another formula from Amazon Herb Company) that contains many herbs known for their ability to stimulate blood and lymphatic circulation's, Envirozon that assists liver functions, and Arcozon that assists immune functions. In addition to these herbs, Gravizon also contains strong antioxidants that provide protection against free radicals. For example, cam camu, a small fruit the size of a large cherry that contains up to 4,000 times the amount of Vitamin C contained in on orange. Also, sangre de drago, the sap of a tree that is nearly 90% oligomeric proanthocyanidins, the active component in grapeseed extract. Therefore, Gravizon is a unique formula designed to provide unique immune support to assist the body in regaining and maintaining health. March, 2003 update on Anne Caputi: "I had my 6th follow-up MRI this morning. Next week is the one year anniversary of my brain surgery. Another perfectly clear scan! Then I got my tumor markers. The lowest they have ever been in almost six years . I don't remember the first time we tested them, but as of last week, my CEA is 5.5, (normal is 0-4) and my CA27-29 is down this month, from 121 in February to 90 currently! They really don't know what to make of me. I enjoy keeping this going. Still, no one asks my secret." **Anne Caputi died of metatastic breast cancer in November 2006. She lived for many years fighting this disease. Graviola "In an 1976 plant screening program by the National Cancer Institute, the leaves and stem of Graviola showed active cytotoxicity against cancer cells and researchers have been following up on this research ever since. Much of the research on Graviola focuses on a novel set of phytochemicals called annonaceous acetogenins. The potent antitumor, pesticidal and/or insect antifeedant properties of these annonaceous acetogenins have been reported and patented. Graviola produces these natural compounds in leaf, bark and twig tissues, and they have be documented to possess both highly anti-tumor and pesticidal properties. Mode of action studies in three separate laboratories have recently determined that acetogenins are superb inhibitors of Complex I in mitochondrial electron transport systems from several organisms including tumors. Research on various Annona species of plants has yielded many extremely potent acetogenins. Many of them have cytotoxicity with ED50 values as low as 10-9 ug/ml. Active compounds from Graviola and other Annona plants have been submitted to the NIH anti-AIDS screen by Purdue University and their work is continuing with a number of other active plant species in the Annona plant family. Thus far, Purdue and/or it's staff have filed at least 9 U.S. and/or international patents on their work around the antitumorous and insecticidal properties and uses of these acetogenins. Three separate research groups have isolated novel compounds in the seeds and leaves of Graviola which have demonstrated significant anti-tumorous, anticancerous and selective toxicity against various types of cancer cells, publishing 8 clinical studies on their findings. One study demonstrated that an acetogenin in Graviola was selectively cytotoxic to colon adenocarcinoma cells in which it was 10,000 times the potency of adriamycin (a chemotherapy drug). Cancer research is ongoing on Graviola, and four new studies have been published in 1998 which further narrow down the specific phytochemicals which are demonstrating the strongest anticancerous and antiviral properties. Annonaceous acetogenins are only found in the Annonaceae family. In general, various annonaceous acetogenins have been documented with antitumor, antiparasitic, pesticidal, antiprotozoal, antifeedant, anthelmintic, and antimicrobial activities. There has been much interest in the chemicals which have demonstrated potent antitumor properties and several research groups are trying to synthesize these chemicals for new chemotherapeutic drugs. In a review of these natural chemicals in The Journal of Natural Products in 1999 they noted: "The Annonaceous acetogenins are promising new antitumor and pesticidal agents that are found only in the plant family Annonaceae. Chemically, they are derivatives of long-chain fatty acids. Biologically, they exhibit their potent bioactivities through depletion of ATP levels via inhibiting complex I of mitochondria and inhibiting the NADH oxidase of plasma membranes of tumor cells. Thus, they thwart ATP-driven resistance mechanisms." Another review in the Skaggs Scientific Report 1997-1998 states, "Annonaceous acetogenins, particularly those with adjacent bis-tetrahydrofuran (THF) rings, have remarkable cytotoxic, antitumor, antimalarial, immunosuppressive, pesticidal, and antifeedant activities. Many of these fatty acid derivatives have similar carbon skeletons; their striking diversity originates mainly from the relative and absolute configuration of their various stereogenic oxygen functions." Purdue University has conducted a great deal of research on annonaceaous acetogenins, much of which has been funded by The National Cancer Institute and/or the National Institute of Health. In one of their reviews titled Recent Advances in Annonaceous Acetogenins, they state: "Annonaceous acetogenins are waxy substances consisting of C32 or C34 long chain fatty acids which have been combined with a 2-propanol unit at C-2 to form a lactone. They are only found in several genera of the plant family, Annonaceae. Their diverse bioactivities as antitumor, immunosuppressive, pesticidal, antiprotozoal, antifeedant, anthelmintic, and antimicrobial agents, have attracted more and more interest worldwide. Recently, we reported that the Annonaceous acetogenins can selectively inhibit the growth of cancerous cells and also inhibit the growth of adriamycin resistant tumor cells. As more acetogenins have been isolated and additional cytotoxicity assays have been conducted, we have noticed that, although most of acetogenins have high potencies among several solid human tumor cell lines, some of the derivatives within the different structural types and some positional isomers showed remarkable selectivities among certain cell lines, e.g., against prostate cancer (PC-3). We now understand the primary modes of action for the acetogenins. They are potent inhibitors of NADH: ubiquinone oxidoreductase, which is in an essential enzyme in complex I leading to oxidative phosphorylation in mitochondria. A recent report showed that they act directly at the ubiquinone-catalytic site(s) within complex I and in microbial glucose dehydrogenase. They also inhibit the ubiquinone-linked NADH oxidase that is peculiar to the plasma membranes of cancerous cells." In 1997, Purdue University published information with promising news that several of the Annonaceous acetogenins: "not only are effective in killing tumors that have proven resistant to anti-cancer agents, but also seem to have a special affinity for such resistant cells." In several interviews after this information was publicized, the head Purdue pharmacologist in Purdue's research explains that cancer cells that survive chemotherapy may develop resistance to the agent originally used against them as well as to other, even unrelated, drugs. "The term multi-drug resistance (MDR) has been applied to this phenomenon," he says. He explains that such resistance develops in a small percentage of cancer cells when they develop a "P-glycoprotein mediated pump" capable of pushing anti-cancer agents out of the cell before they can kill it. Normal cells seldom develop such a pump. "If having this pump was such a good deal, all cells would have it. But all cells don't," the Purdue researcher says. "In a given population of cancer cells in a person, maybe only 2% of the cancer cells possess this pump. But it's those 2% of cancer cells that eventually grow and expand to create drug-resistant tumors." They go on to say that some studies have tried to bypass these pumps by keeping them busy with massive doses of other drugs, like the blood pressure agent verapamil. In this way, it was hoped that some of the anti-cancer drugs would enter the cell and destroy it. But this only caused potentially fatal side effects such as loss of blood pressure. In the June issue of Cancer Letters, the Purdue researchers reported that the Annonaceous acetogenin, bullatacin, preferentially killed multi-drug resistant cancer cells because it blocked production of adenosine triphosphate, ATP -- the chief energy-carrying compound in the body. "A multi-drug resistant cell requires a tremendous amount of energy to run the pump and extrude things out of the cell," Purdue head pharmacolgist says. "By inhibiting ATP production, we're essentially pulling the plug on its energy source." But what about the effect on ATP in normal cells? "Normal cells and standard cancer cells may be able to minimize the effect of this compound because they don't require vast amounts of energy needed by the pump-running cells," the Purdue researcher says. "The resistant cell is using its extra energy for this pump as well as to grow, so it is really taxed for energy. When we mess with the energy supply, it kills the cell!" Original Source: Dr. Leslie Taylor, ND, Raintree Nutrition, Inc. and Square One Publishers, Customer Service Raintree Nutrition, Inc. 3579 Hwy 50 East, Suite 222 Carson City, Nevada USA (775) 841-4142 (800) 780-5902 Fax: (775) 841-4022 Website: http://www.rain-tree.com Richard Lund: "We, like you, are not doctors, so we cannot dispense medical advice. But we do try to educate people about Paw Paw's actions to slow ATP production in abnormal cells in the body. Our toll free number is 877-871-6262. The web address for sale of the Paw Paw twig extract is pawpawforhealth.com. The material largely applies to Paw Paw as well as to Graviola. They both contain the Annonaceous acetogenins. In fact, the one acetogenin mentioned, bullatacin, does not occur in Graviola. It was first isolated from Annona bullata by Dr. McLaughlin and has been found in Paw Paw as well as some of the other Annonaceous family, but not in Graviola." LINK to source for Graviola and information LINK to source for graviola LINK to source used by Anne Caputi Posted September, 2005 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.