The purpose of this site is to collect lab research by medical doctors about herbs that are proven to treat illnesses and counter the false attacks on herbs by the medical industry and false claims by alternative medicine. I let the science tell the facts.
 
index sitemap advanced
search engine by freefind
 

Pawpaw Root (Asimina triloba)

kills Prostrate Cancer

This page has a collection of 23 research reports showing Pawpaw root kills prostate cancer hundreds, thousands, and even up to 100 million times the leading chemo drug of adriamycin   see report #7 by Perdue University below

The facts on this page are indicative of the power of natural compounds vs the dangerous side effects of altered drugs. The medical industry is ignoring these scientifically proven medical facts proven by doctors and not telling us about them. There is only one reason our doctors are not telling us about them and that is the compelling power of the drug companies through the FDA to protect their profits at the expense of our lives. Did you know their power is excerted by our government through the FDA who will not allow doctors to prescribe herbs even when they are proven to be better and safer. If you or I had a life saving product that would save the life of dying people and failed to tell them about it would not the courts hold us liable? For example have not the courts many times held persons and companies liable for creating a product that was unsafe?

Annonaceous acetogenins are powerful anticancer chemicals found in the Annonaceae family of trees (usually called Pawpaw, Soursop, Custard-apple or Graviola trees). These chemicals are in high concentrations throughout the tree including the fruit (over 2% of the dry weight of the fruit is Annonaceous acetogenins see research # 3 below). The fruit is very tangy and delicious and eaten daily (anticancer chemicals and all) by many people in some parts of the world (it is the South American equivalent of Lemonade in the US). Annonaceous acetogenins are nontoxic (and tasty) and used medically in South America. For anyone that is wondering, yes this is the same Pawpaw that Baloo the bear in Walt ‘Disney’s animated movie “The Jungle book” sings about in the song “The Bare Necessities”...Doxorubicin and Adriamycin are toxic Anthracycline type drugs and are among the most effective cancer killing chemotherapy drugs used by Drs. Unfortunately they are also among the most toxic and are very destructive to your heart. If the Drs. are trying to use them on you, kiss your heart goodbye. (see research #1 & 2)...Anthracyclines are among the most powerful, effective and toxic chemotherapy drugs used on “Multiple Drug Resistant” (MDR) cancer (see research # 1 & 2) so Annonaceous acetogenins are commonly tested against Anthracyclines (see # 6--22 below). Most people find it hard to believe that Pawpaw can be so many times more effective than a FDA approved Chemo super drug, so medical research is provided to prove it. To get a feel of how much more powerful Pawpaw chemicals are than chemotherapy drugs, look at research summary #7, #17, #19 and #22.. potency of over 100 million times that of Adriamycin (Notice this is even a very respected American medical research center saying this)

Will Annonaceous acetogenins kill all cancer?
 NO, Annonaceous acetogenins
work by various methods to block cancer cells from getting the ATP (energy) produced by Mitochondria that is needed by cancer for fast growth and or defense from chemotherapy and radiation (see # 4 & 5). Annonaceous acetogenins have little effect on slow growing and easy to kill cancer because the amount of ATP needed by these cancers is only a little more than needed by healthy cells. Also some energy dependant cancers can make enough energy without using the Mitochondria to survive. However many fast growing or Multiple Drug Resistant (MDR) cancers have high ATP needs and are dependant on Mitochondria. These cancers are hit extremely hard by Annonaceous acetogenins without affecting normal cells (see # 21). The effect of Annonaceous acetogenins on Mitochondria dependant cancer that is both fast growing and MDR is absolutely amazing!

Caution;
 Driving a car or operating machinery while on very high doses is as dangerous as taking Valium.

Toxicity;
 This is a part of the diet of millions of people and it took some digging to find any problems. However high consumption of Annonaceous acetogenins for several decades can interfere with brain ATP needs in some people and cause a type of Parkinson’s disease (see# 23). This is very rare even with heavy long-term usage so several months usage to kill cancer is very safe.

Are Annonaceous acetogenins available?
 Yes but no single Annonaceae tree has all types so it takes a combination. Annona muricata (sometimes called Amazon Pawpaw or Graviola) and Asimina triloba (commonly called American Pawpaw) are readily available and between them should contain all of the Annonaceous acetogenins tested in # 6—22 below."

Below are 23 scientific research reports about Pawpaw and Gaviola Fruit. In order to be as brief as possible only portions of each report are quoted. However anyone who wants to read the actual research report can click the link.  

1. Doxorubicin is one of the most effective chemotherapeutic agents used in the treatment of malignancies. Cardiotoxicity is the most important dose-limiting toxicity of doxorubicin. Although cardiomyopathy is the most well known side effect of doxorubicin, it usually occurs many years after the treatment and relates to cumulative doxorubicin dosage. Another form of doxorubicin cardiotoxicity is arrhythmia which may occur at any time and after any dosage. . copy 15878560 then click PMID and paste the number in their search box

 2: This report shows the dangers of chemo drugs "...Anthracycline-induced cardiotoxicity in children with cancer ...The fact that anthracyclines are cardiotoxic seriously narrows their therapeutic index in cancer therapy. The cardiotoxic risk increases with the cumulative dose and may lead to congestive heart failure (CHF) and dilated cardiomyopathy in adults and in children. The prevention of anthracycline-induced cardiotoxicity is particularly important in children who can be expected to survive for decades after being cured of their malignancy...In the presence of CHF, recovery with digitalis-diuretic therapy alone seldom occurs, and in patients who have refractory hemodynamic decompensation, heart transplantation is indicated. copy 15871628 then click PMID and paste the number in their search box

3: Various plant parts of the paw paw tree (Asimina triloba Dunal, Annonaceae) were extracted and partitioned to concentrate the mixture of acetogenins into a standardized pesticidal extract (F005). A bioassay with brine shrimp larvae (Artemia salina Leach) was used to determine the relative potencies of the various extracts. The small twigs (0-0.5 cm diameter) yielded the most potent extract (LC50 = 0.04 ppm); the stem wood (LC50 = 4.9 ppm) and leaves (LC50 = 53.7 ppm) yielded the poorest activities. The unripe fruits, seeds, root wood, root bark, and stem bark were notably potent and, generally, yielded > 2% of their dry weight as F005. The smaller diameter stems were more potent than the larger stems.  copy 1464691 then click PMID and paste the number in their search box
 
4: 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. copy 10096871 then click PMID and paste the number in their search box
 
5: "ATP depletion is the mode of action of the Annonaceous acetogenins, and these agents offer a special advantage in the chemotherapeutic treatment of MDR tumors that have ATP-dependent mechanisms. copy 9097981 then click PMID and paste the number in their search box

6:  Bioactivity-directed fractionation of the seeds of Asimina triloba resulted in the isolation of asimitrin (1) and 4-hydroxytrilobin (2). Compounds 1 and 2 showed cytotoxic selectivity, with 100-10,000 times the potency of adriamycin against prostate adenocarcinoma (PC-3) and colon adenocarcinoma (HT-29) cell lines. copy 15730242 then click PMID and paste the number in their search box
 

7: "The bark extracts of Annona squamosa yielded a new bioactive acetogenin, squamotacin (1), and the known compound, molvizarin (2), which is new to this species. Compound 1 is identical to the potent acetogenin, bullatacin (3), except that the adjacent bistetrahydrofuran (THF) rings and their flanking hydroxyls are shifted two carbons toward the gamma-lactone ring. Compound 1 showed cytotoxic selectively for the human prostate tumor cell line (PC-3), with a potency of over 100 million times that of Adriamycin. "   http://www.ncbi.nlm.nih.gov/pubmed?term=8991957
 

8: "Systematic synthesis of mono- and bis-THF ring cores, synthetic intermediates of antitumor annonaceous acetogenins, has been achieved by asymmetric alkynylation and subsequent stereodivergent THF ring formatio Systematic synthesis of mono- and bis-THF ring cores, synthetic intermediates of antitumor annonaceous acetogenins, has been achieved by asymmetric alkynylation and subsequent stereodivergent THF ring formation as key steps. The asymmetric alkynylation of alpha-oxyaldehyde and alpha-tetrahydrofuranic aldehyde with (S)-3-butyne-1,2-diol derivatives gave good yield with very high diastereoselectivity. These adducts were converted into mono- and bis-THF cores via two kinds of one-pot THF ring formation, respectively. In addition, the total synthesis of murisolin, which shows cytotoxic activity against human tumor cell lines with potency from 10(5) to 10(6) times that of adriamycin, was also achieved."   copy 15467275 then click PMID and paste the number in their search box

9: " Annonaceous acetogenins have potent antitumor effect in vitro and in vivo. Squamocin is one of the annonaceous acetogenins and has been reported to have antiproliferative effect on cancer cells. Our results from this study showed that squamocin inhibited proliferation of HL-60 cells with IC50 value of 0.17 microg/ml and induced apoptosis of HL-60 cells. Investigation of the mechanism of squamocin-induced apoptosis revealed that treatment of HL-60 cells with squamocin resulted in extensive nuclear condensation. DNA fragmentation, cleavage of the death substrate poly (ADP-ribose) polymerase (PARP) and induction of caspase-3 activity. Pretreatment of HL-60 cells with caspase-3 specific inhibitor DEVD-CHO prevented squamocin-induced DNA fragmentation, PARP cleavage and cell death. The expression levels of protein bcl-2, bax have no change in response to squamocin treatment in HL-60 cells, whereas stress-activated protein kinase (SAPK/JNK) was activated after treatment with squamocin in HL-60 cells. These results suggest that apoptosis of HL-60 cells induced by squamocin requires caspase-3 activation and is related to SAPK activation".  copy 11883704 then click PMID and paste the number in their search box

10: " A novel and two known bioactive mono-tetrahydrofuran (THF) annonaceous acetogenins, annomocherin (1), annonacin (2) and annomontacin (3), have been isolated from the fractionated ethanolic extracts of the seeds of Annona cherimolia, guided by the brine shrimp lethality test (BST). Their structures were elucidated on the basis of spectroscopic and chemical methods. All compounds have a relative stereochemistry of threo/trans/threo for the mono-THF ring with two flanking hydroxyls. Compound 1 has a double bond at C-23/24 of aliphatic chain. Compound 1 was isolated from natural sources for the first time, and was named annomocherin. Two known Compounds 2 and 3 which have never been isolated from this species before, were obtained. Compound 1 exhibited potent and selective cytotoxicities against the breast carcinoma (MCF-7) and kidney carcinoma (A-498) cell lines with 100 to 1,000 times the potency of adriamycin. In brine shrimp lethality test (BST), 1-3 exhibited cytotoxicity."
 copy 11534761 then click PMID and paste the number in their search box

11: "  Two new cytotoxic annonaceous acetogenins, named uvarigrin(1) and uvarigrandin A(3), were obtained from the roots of Uvaria grandiflora Roxb(Annonaceae). Based on X-ray analysis and Mosher's methodology, the overall absolute configuration of 1 was established as 15S, 17R, 18R, 21R, 22R, 36S. The absolute configuration of 3 was also resolved by Mosher's methodology. The relative configuration of the previously reported uvarigranin (2) was revised. Compound 1 showed cytotoxicity against HCT-8, Bel7402 and A2780 human tumor cell lines at ED50 levels of 0.15, 0.21 and 0.41 microgram.ml-1, respectively. "
copy 11499032 then click PMID and paste the number in their search box

 12: " Two new cytotoxic annonaceous acetogenins, annomolin (1) and annocherimolin (2), were isolated from an ethanolic extract of the seeds of Annona cherimolia. Annomolin has a mono-THF ring with one flanking hydroxyl and possesses a 1,2-diol at C-7/8 of the aliphatic chain. Annocherimolin has a mono-THF ring with two flanking hydroxyls and possesses a double bond at C-21/22. Their structures were elucidated by spectral data and chemical derivatization. Compound 1 showed cytotoxic selectivity for the human prostate tumor cell line (PC-3), with a potency of over 10,000 times that of adriamycin. Compound 2 showed cytotoxic potencies about 10,000 times those of adriamycin in the breast (MCF-7) and colon (HT-29) cancer cell lines.copy 11325235 then click PMID and paste the number in their search box

13: " Asitrocin (1) and the mixture of (2,4)-cis- and trans-asitrocinones (2 and 3), new bioactive Annonaceous acetogenins, were isolated from the seeds of Asimina triloba by activity-directed fractionation using the brine shrimp lethality test. Asitrocin and the mixture of (2,4)-cis- and trans-asitrocinones have a configuration of erythro/trans/threo from C-15 to C-20, the mono-THF moiety with two flanking hydroxyl groups. The structures were determined by spectroscopic methods. These acetogenins showed potent bioactivities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the prostate (PC-3) and the pancreatic (MIA PaCa-2) cell lines at 10-100 times the potency of adriamycin. "  copy 11087592 then click PMID and paste the number in their search box

 14: " cis-Annonacin (1) and the mixture of (2,4)-cis-and trans-isoannonacins (2 and 3), three known mono-tetrahydrofuran annonaceous acetogenins, have been isolated from the seeds of Annona cherimolia by the use of the brine shrimp lethality test (BST) for bioactivity directed fractionation. Their structures were elucidated based on spectroscopic and chemical methods. 1 showed potent cytotoxicities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the pancreatic cell line (PaCa-2) at about 1,000 times the potency of adriamycin. The mixture of 2 and 3 is over 10,000 times cytotoxic as adriamycin in the pancreatic cell line (PaCa-2). All of the compounds are about 10 to 100 times as cytotoxic as adriamycin in the prostate cell line (PC-3). copy 10549583 then click PMID and paste the number in their search box

 15: " Two new bioactive Annonaceous acetogenins, annoglaxin (1) and 27-hydroxybullatacin (2), have been isolated from the fractionated ethanolic extracts of the leaves of Annona glabra, directing the fractionation with the brine shrimp lethality test (BST). The structures of 1 and 2 were elucidated on the basis of spectroscopic and chemical methods, and the absolute stereochemistries were determined by the advanced Mosher ester method. 1 presents unusual features of an OH at C-8 and a carbonyl at C-12 and, while less potent than 2, shows interesting selectivity for the human breast carcinoma (MCF-7) cell line. Compound 2 was at least 100 000 times more potent than adriamycin against the human kidney carcinoma (A-498), prostate carcinoma (PC-3), and pancreatic carcinoma (PACA-2) cell lines in our panel of six human solid tumor cell lines."   copy 10395501 then click PMID and paste the number in their search box

 16: "The seeds of Asimina triloba have yielded two novel cytotoxic mono-tetrahydrofuran (THF) Annonaceous acetogenins, asitrilobins A (1) and B (2). In addition, annonacin, asimin and asiminacin, which are known, and annomontacin and xylomaticin, which are known but are new in this species, were obtained. Compounds 1 and 2 have a relative stereochemical relationship of erythro/cis/threo across the mono-THF ring with its two flanking hydroxyls and they, thus, represent a new type of acetogenin. Their structures were established on the basis of chemical and spectral evidence. 1 and 2 showed potent bioactivities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the pancreatic cell line (MIA PaCa-2) at ten to one-hundred times the potency of adriamycin. "  copy 10385998 then click PMID and paste the number in their search box

 17: "Continuing work on the bioactivity-directed fractionation of the bark of Annona squamosa has resulted in the discovery of three new Annonaceous acetogenins, (2,4-cis and trans)-squamolinone (1), (2,4-cis and trans)-9-oxoasimicinone (2), and bullacin B (3). Compounds 1-3 are all adjacent bis-THF ring acetogenins with 2 representing the first bis-ring acetogenin to contain a carbonyl along its aliphatic chain. Compound 3 was selectively cytotoxic in a panel of six human tumor cell lines with a potency of nearly a million times that of adriamycin against the MCF-7 (human breast adenocarcinoma) cell line."   copy 9629470 then click PMID and paste the number in their search box

18: "Fourteen structurally diverse Annonaceous acetogenins, representing the three main classes of bis-adjacent, bis-nonadjacent, and single-THF ring(s), were tested for their ability to inhibit the growth of adriamycin resistant human mammary adenocarcinoma (MCF-7/Adr) cells. This cell line is resistant to treatment with adriamycin, vincristine, and vinblastine and is, thus, multidrug resistant (MDR). Among a series of bis-adjacent THF ring acetogenins, those with the stereochemistry of threo-trans-threo-trans-erythro (from C-15 to C-24) were the most potent with as much as 250 times the potency of adriamycin. A spacing of 13 carbons between the flanking hydroxyl of the THF ring system and the gamma-unsaturated lactone seems to be optimum with a spacing of 11 and 9 carbons being significantly less active. Several single-THF ring compounds were also quite potent with gigantetrocin A (11) being the most potent compound tested. The acetogenins may, thus, have chemotherapeutic potential, especially with regard to MDR tumors."   copy 9207950 then click PMID and paste the number in their search box

19: "Trilobalicin (1), a new nonadjacent bis-THF ring annonaceous acetogenin, 2,4-cis- (2) and 2,4-trans-trilobacinone (3), the ketolactones of trilobacin, an adjacent bis-THF ring acetogenin, were isolated from the stem bark of Asimina triloba (L.) Dunal (Annonaceae). Their structures were established based on hemical and spectral evidence. The relative stereochemistry of 1 was determined as trans/threo/threo/trans/erythro from C-10 to C-22 by comparisons of NMR data with those of model compounds. Compound 1 is the first example of a nonadjacent bis-THF acetogenin being isolated from the title species and represents a new type of these compounds. Bioactivities of these new structures against brine shrimp larvae and six human solid tumor cell lines were determined, and cytotoxic selectivities were shown for the lung (A-549) and breast (MCF-7) cel lines with up to a million times the potency of adriamycin. "  copy 9113328 then click PMID and paste the number in their search box

 20: "Two novel bioactive ketolactone Annonaceous acetogenins, (2,4-cis)-asimicinone (1) and (2,4-trans)-asimicinone (2), have been isolated from Asimina triloba (Annonaceae) by bioactivity directed fractionation. The separation of these two epimeric compounds was achieved by HPLC methods using a Si gel normal phase column eluted with acetone in hexane gradients. The assignments of cis or trans stereochemistry of the ketolactone moieties were made on the bases of 1H-1H COSY and NOESY experiments. 1 and 2 showed selective cytotoxicities against A-549 (human lung cancer) and MCF-7 (human breast cancer) cell lines with ED50 values as low as < 10(-7) micrograms/ml with 2 being the more active isomer."
copy 8743934 then click PMID and paste the number in their search box

 21: Purdue University " 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."   copy 7553608 then click PMID and paste the number in their search box

22: Purdue University "Longicin [1] and (2,4-cis and trans)-goniothalamicinone [2], two new monotetrahydrofuran Annonaceous acetogenins, have been isolated from the leaves and twigs of Asimina longifolia (the long leaf paw paw) by the use of the brine shrimp lethality test for bioactivity-directed fractionation. The structures were elucidated based on spectroscopic and chemical methods. Compound 1 was converted to its ketolactone isomer, (2,4-cis and trans)-longicinone [3], to aid the stereochemical elucidation of 1. Compounds 1-3 showed selective and potent cytotoxicities to certain human tumor cell lines, with the potency of 1 against pancreatic carcinoma (PaCa-2) over one million times that of adriamycin. Nine known cytotoxic acetogenins, annonacin, xylomaticin, isoannonacin, gigantetrocins A and B, muricatetrocins A and B, gigantetrocin-A-one and goniothalamicin, were also isolated for the first time from this species."  copy 7494147 then click PMID and paste the number in their search box

23: Hopital de la Salpetriere, Paris, France. "In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata. These plants contain a class of powerful, lipophilic complex I inhibitors, the annonaceous acetogenins. To determine the neurotoxic potential of these substances, we administered annonacin, the major acetogenin of A. muricata, to rats intravenously with Azlet osmotic minipumps (3.8 and 7.6 mg per kg per day for 28 days). Annonacin inhibited complex I in brain homogenates in a concentration-dependent manner, and, when administered systemically, entered the brain parenchyma, where it was detected by matrix-associated laser desorption ionization-time of flight mass spectrometry, and decreased brain ATP levels by 44%. In the absence of evident systemic toxicity, we observed neuropathological abnormalities in the basal ganglia and brainstem nuclei. Stereological cell counts showed significant loss of dopaminergic neurones in the substantia nigra (-31.7%), and cholinergic (-37.9%) and dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32)-immunoreactive GABAergic neurones (-39.3%) in the striatum, accompanied by a significant increase in the number of astrocytes (35.4%) and microglial cells (73.4%). The distribution of the lesions was similar to that in patients with atypical parkinsonism. These data are compatible with the theory that annonaceous acetogenins, such as annonacin, might be implicated in the aetiology of Guadeloupean parkinsonism and support the hypothesis that some forms of parkinsonism might be induced by environmental toxins."
copy 14675150 then click PMID and paste the number in their search box


 
Recommended Information