===== PAGE 1 ===== ## A cetogenin U pdate Kirk W. Pomper, Ph.D. Principal Investigator of Horticulture/ Kentucky State University A djunct A assistant Professor of Horticulture/ Univ. of Kentucky ===== PAGE 2 ===== ## Disclaimer The following information is for educational purposes only and is not intended for the mitigation, cure or treatment of medical conditions. KSU does not endorse any products by any companies ===== PAGE 3 ===== ## 2011 Estimated US Cancer Deaths
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26% Lung & bronchus 15% Breast 9% Colon & rectum 7% Pancreas 6% Ovary 4% Non-Hodgkin lymphoma 3% Leukemia 3% Uterine corpus 2% Liver & intrahepatic bile duct 2% Brain/Other nervous system 23% All other sites ===== PAGE 4 =====
The Lifetime Probability of Developing Cancer for Men, 2005-2007*
SiteRisk
All sites\dagger1 in 2
Prostate1 in 6
Lung and bronchus1 in 13
Colon and rectum1 in 19
Urinary bladder\ddagger1 in 26
Melanoma\S1 in 37
Non-Hodgkin lymphoma1 in 43
Kidney1 in 53
Leukemia1 in 66
Oral Cavity1 in 71
Stomach1 in 91
* For those free of cancer at beginning of age interval. † All Sites exclude basal and squamous cell skin cancers and in situ cancers except urinary bladder.\ddagger Includes invasive and in situ cancer cases § Statistic for white men. Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.5.0 Statistical Research and Applications Branch, NCI, 2010. http://srab.cancer.gov/devcan ===== PAGE 5 =====
The Lifetime Probability of Developing Cancer for Women, 2005-2007*
SiteRisk
All sites\dagger1 in 3
Breast1 in 8
Lung & bronchus1 in 16
Colon & rectum1 in 20
Uterine corpus1 in 39
Non-Hodgkin lymphoma1 in 52
Urinary bladder\ddagger1 in 87
Melanoma\S1 in 55
Ovary1 in 72
Pancreas1 in 71
Uterine cervix1 in 147
* For those free of cancer at beginning of age interval. † All Sites exclude basal and squamous cell skin cancers and in situ cancers except urinary bladder.\ddagger Includes invasive and in situ cancer cases § Statistic for white women. Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.5.0 Statistical Research and Applications Branch, NCI, 2010. http://srab.cancer.gov/devcan ===== PAGE 6 ===== ## A cetogenin Compounds and Cancer: Research at Purdue University
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Dr. Jerry M cL aughlin Professor of pharmacognosy Extracts of pawpaw were are among the most potent of the 3500 species of higher plants screened for bioactive compounds in his laboratories ===== PAGE 7 ===== ## Paw paw A cetogenin Compounds A nnonaceous acetogenins Long unbranched fatty acid chain over 50 unique annonaceous acetogenins
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A simicin Inhibitor of complex I of the mitochondrial respiratory chain. Present in young paw paw twig and other tissues Bullaticin
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===== PAGE 8 ===== ## A nti-tumor A ctivity
Table 1. The bioactivities of bullatacin in the brine shrimp test and human solid tumor cell lines.
CompoundBST LC50 (μ g/ml)ED50 (μ g/ml)MCF-7 ED50 (μ g/ml)HT-29 ED50 (μ g/ml)
Bullatacin1.59 × 10-31.25 × 10-13>101.0 × 10-12
Adriamycin2.57 × 10-11.04 × 10-41.76 × 10-21.53 × 10-4
BST = brine shrimp lethality test A -549 = human hung carcinorma Adriamycin textcircled R = standard anticarcinoma drug MCF -7 = human breast carcinoma ED 50 = effective dose resulting in 50% cell death HT-29 = human colon carcinoma LC 50 = lethal concentration resulting in 50% deaths ===== PAGE 9 ===== ## Paw paw A cetogenin Compounds The powerful cytotoxicity, in vivo antitumor, pesticidal, antimalarial, antiviral, and antimicrobial effects indicated a myriad of potentially useful applications. Commercial development of these compounds shampoo, highly effective in treating infestations of head lice, fleas, and ticks. pesticidal sprays, which protects host plants against a diversity of pests. an ointment for treatment of oral herpes (HSV-1) and other skin afflictions. The extract (in capsule form) has been used by certain cancer patients as a botanical supplement product. ===== PAGE 10 ===== ## NATURE'S SUNSHINE United States search Customer Service 1-800-223-8225 shopping cart ## Ordering Tools
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## Customer Favorites You have in your shopping cart: 0 products: 0.00 + A-ZProduct Listing Weekly Specials Top Sellers Super Trio JumpStart Packs Health Assessment ## Core Health - Nutrition New Products Probiotics < div style = "text-align: center;" > < img src = "imgs/imginimagebox62911057701165.jpg" alt = "Image" width = "4%" / > < /div > Antioxidants < div style = "text-align: center;" > < img src = "imgs/imginimagebox62615247671579.jpg" alt = "Image" width = "4%" / > < /div > ## Paw Paw Cell-Reg™ (180 caps) < div style = "text-align: center;" > < img src = "imgs/imginimagebox99796112221364.jpg" alt = "Image" width = "7%" / > < /div > Stock Number: 515-6 Retail Cost:59.95 Member Cost: $39.95 Qty: ___ 1 add to cart ## View Product Guide View Product Label ·Selectively affects specific cells. •Modulates the production of ATP in mitochondria of specific cells. •May help modulate the growth of blood vessels near specific cells. Paw Paw Cell-RegTM [Immune]. Because health begins in the body's cells, it is important to support the health of all cells. Paw Paw Cell-Reg is a unique product that selectively targets specific cells to enhance the overall health of the body. Over 50 active compounds exist in Paw Paw Cell-Reg and these complex chemicals are called acetogenins. Acetogenins affect the production of ATP in the mitochondria (the powerhouse) of the cell. ATP is the major source of cellular energy. By selectively modulating the production of ATP in specific cells, the acetogenins affect the viability of specific cells and the growth of blood vessels that nourish them. A clinical study with over 100 participants showed that the paw paw extract, containing a Read more... ===== PAGE 11 ===== ## Botany and Genetic Resources ## Asimina triloba is a member of the tropical Custard Apple or Annonaceae family custard apple (Annona reticulata L.)
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cherimoya (A. cherimola Mill.) sweetsop or sugar apple (A. squamosa L.) atemoya (A. squamosa x A. cherimola) soursop (A. muricata L.)
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===== PAGE 12 ===== ## Consumption of Annona fruit and teaA Link to Parkinsonism? Caparros-L efebvre and Elbaz (1999) reported in Guadeloupe, atypical parkinsonism was abnormally frequent, and represented 75% of progressive parkinsonism while Parkinson's disease accounted for only 25% of the cases. inversed percentage in comparison with patients living in Europe and North America. A higher proportion of patients with atypical parkinsonism (consumed soursop fruit 97%; consumed herbal tea 83%) than patients with Parkinson's disease (fruit 59%; herbal tea 18%) or control with no Parkinson symptoms (fruit 60%; herbal tea 43%). ===== PAGE 13 ===== ## Consumption of an A cetogen Compound-A nonacin Champy et al. (2005) determined the concentrations of annonacin, the major acetogenin in soursop. An average fruit contains about 15 mg of annonacin. When directly injecting rats for one month with the estimated amounts of annonacin ingested in a year by eating one fruit daily, this induced neurodegeneration in the basal ganglia and mesencephalon (Champy et al., 2004). Purified extract and bioavailability upon digestion not examined. ===== PAGE 14 ===== ## Consumption of Annona fruit and tea-A Link to Parkinsonism? The prevalence of Parkinson's disease is roughly 150 per 100,000 inhabitants in the United States or Europe (Schrag et al., 1999). Caparros-L efebvre et al. (2005) calculated that the number of PD cases in Guadeloupe would be approximately 640 (out of 420,000 people) 152 per 100,000 Y ounger people who had symptoms and stopped consuming Annona products reversed their symptoms ===== PAGE 15 ===== ## A typical Parkinsonism in Guadeloupe Sensitivity to acetogenin compounds may be limited to those with a specific genetic predisposition in Guadeloupe The H2 allele has been reported to carry variants that are protective PSP and is rare (5% vs. 20%) in the Guadeloupian population may contribute, in association with unidentified genetic or environmental risk factors, to disease susceptibility (Camuzat et al., 2008). ===== PAGE 16 =====
Table 1. Brine shrimp lethality and percentage yields of F005 (90% aqueous methanol fraction) from various plant parts of Asimina triloba.
Plant part extractedLC50 (ppm)2Yield of F005 (%)
Twigsy0.042 (0.02-0.09)1.78
Unripe fruitx0.060 (0.03-0.08)5.11
Root woodw0.060 (0.03-0.08)1.27
Seedv0.065 (0.03-0.10)4.03
Stem barkx,u0.077 (0.04-0.12)2.71
Stem barky,u0.102 (0.06-0.15)1.96
Stem barky0.104 (0.03-0.20)2.52
Root barkw0.135 (0.09-0.21)2.72
Whole stem: wood, bark and leavesy0.202 (0.14-0.31)1.60
Stem woody4.86 (0.37-11.93)0.90
Leavesy53.6 (33-82)4.36
Ratnayake, S., J.K. Rupprecht, W.M. Potter, and J.L. M cL aughlin. 1993.
===== PAGE 17 ===== ## Objective To determine if extracts of ripe pawpaw fruit pulp display acetogenin activity. ===== PAGE 18 ===== ## Brine Shrimp Lethality Assay (BST) Artemia saline or Sea M onkeys Rapid, in house, and low cost substitute for cytotoxic assays developed by Dr. M cL aughlin Responsible for the isolation of numerous, chemical and pharmacologically diverse antitumor and pesticidal compounds. Records the lethal concentration to kill 50% of the shrimp (L C50 value with upper and lower 95% confidence levels) ===== PAGE 19 ===== ## Brine Shrimp Test-A cetogenin Activity A bout nine grams of paw paw pulp was extracted with ethanol and concentrated through a series of methanol and chloroform extractions as described by Ratnayake et al., (1993). Twenty brine shrimp larvae, taken 48 h after initiation of hatching in artificial sea water were added to each vial (5mL) containing 0, 10, 100 and 1000 ppm concentrations of extract. A after 24 h, survivors were counted. SD from three extracts. ===== PAGE 20 =====
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===== PAGE 21 =====
Table 3. Brine Shrimp Mortility (LC50) Values for the Pawpaw Cultivars 'Mitchell', 'NC-1', 'Overleese', 'Zimmerman', 'Wells', and 'Sunflower' from Frozen Pulp of Ripe Fruita
pawpaw cultivarLC50 (ppm)pawpaw cultivarLC50 (ppm)
‘Mitchell’0.31 (± 1.02)‘Zimmerman’4.09 (± 0.49)
‘Overleese’0.38 (± 1.48)‘Wells’7.33 (± 1.27)
‘NC-1’0.89 (± 1.41)‘Sunflower’8.60 (± 0.42)
aParentheses enclose standard error. ===== PAGE 22 ===== ## Confirmation of A cetogenins in ‘NC-1’ Pulp Subjected to HPLC S-M ass Spec A analysis
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===== PAGE 23 ===== ## W hat the FDA Says: K entucky State University asked the U.S. Food and Drug Administration (FDA) for an opinion on this topic, and their conclusion was that pawpaw has a long history of food use and the FDA does not currently have any evidence that pawpaw is unsafe to eat. ===== PAGE 24 =====
Table 1. Highest and Lowest Brine Shrimp Test LC50 Values of Extracts from 135 Individual Paw Paw Trees Growing at the WMREC Plantationa,b
high producerslow producers
tree sampleBST- LC50 (ppm)tree sampleBST- LC50 (ppm)
4-110.033 \pm 0.00102-3232 \pm 12
5-820.053 \pm 0.0151-1912 \pm 4.7
4-700.056 \pm 0.03544-4610 \pm 0.55
2-880.063 \pm 0.0205-148.4 \pm 2.5
a Grand mean LC 50 value of 1.2 ppm ± 0.30 ppm.b Twig samples were collected, September 26, 1995, from trees planted in the spring of 1984. ===== PAGE 25 ===== ## Summary We are screening current paw paw cultivars for acetogenin activity: High: NC-1, Overleese, Mitchell, Middletown, Susquehanna,... Low: Sunflower, W abash, Potomac, Zimmerman, Wells,... In the KSU pawpaw breeding program, we are selecting both high and low acetogenin genotypes. ===== PAGE 26 ===== Questions?