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Laetrile/Amygdalin (PDQ®): Complementary and alternative medicine - Health Professional Information [NCI] - Laboratory / Animal / Preclinical Studies

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In the fourth study, cultured human bladder cancer cells were treated with amygdalin alone or a combination of amygdalin and an antibody that was coupled (chemically) to beta-glucosidase.[20] The target for this antibody was the glycoprotein (a protein with sugar molecules attached) MUC1. Aberrant forms of MUC1 are produced and displayed at high levels on the outside of several types of cancer cells, including bladder cancer cells. In this study, amygdalin alone was not very effective in killing the bladder cancer cells, but its cell-killing ability was 36 times greater in the presence of the antibody-enzyme complex. There are two possible explanations for this increase in cell-killing ability. The first is that antibody-enzyme complexes bound via MUC1 produce high rates of amygdalin breakdown at the cell surface. This breakdown leads to high local production of cyanide, which is quickly taken up by the cells and kills them. The second explanation is that antibody-enzyme complexes bound to the cells are internalized, thereby increasing the intracellular concentration of beta-glucosidase. Increased beta-glucosidase activity inside a cell would result in increased breakdown of amygdalin taken up by it, and increased cyanide production and cell death. These two potential mechanisms are not mutually exclusive. In another experiment, the researchers cultured bladder cancer cells in the presence of human brain tumor cells, which do not express MUC1. When this coculture was treated with amygdalin and the antibody-enzyme complex, the bladder cancer cells were killed selectively. In view of the mechanisms proposed above, this result is not surprising, since the bladder cancer cells and the brain tumor cells in this coculture formed homogeneous colonies (colonies that contained exclusively bladder cancer cells or brain tumor cells). Conceivably, selective killing of some types of human cancer cells might be achievable through application of this method; however, these positive results must be confirmed independently, and the effectiveness of this approach in animal models must be demonstrated before its use in humans can be considered.

The toxicity of laetrile appears to be dependent on the route of administration. Oral administration is associated with much greater toxicity than intravenous, intraperitoneal, or intramuscular injection.[1,6,14,21] Reviewed in [9,10,22,23] As noted previously (refer to the History section of this summary for more information), most mammalian cells contain only trace amounts of the enzyme beta-glucosidase;[24] however, this enzyme is present in gastrointestinal tract bacteria and in many food plants. Reviewed in [6,9,15,25,26,27] Two studies have specifically examined the role of intestinal bacteria in the breakdown of orally administered amygdalin.[9,28] In one study, rats bred and raised under germ-free conditions and rats bred and raised under normal conditions were given oral amygdalin. The germ-free rats exhibited no side effects from the compound, and their blood concentrations of cyanide were indistinguishable from those of untreated rats. Many of the rats with normal quantities of intestinal bacteria showed signs of cyanide poisoning (e.g., lethargy and convulsions), and they had high levels of cyanide in their blood. In the second study, rats were either treated or not treated with the antibiotic neomycin before being given oral amygdalin.[6] In this study, urinary excretion of detoxified cyanide (i.e., thiocyanate) was measured. The amount of urinary thiocyanate was 40 times higher in rats that had not been given the antibiotic, indicating that more amygdalin had been broken down in animals with normal amounts of intestinal bacteria. In humans, as in rats, substantial breakdown of amygdalin occurs in the intestines; however, little breakdown of either intravenously or intramuscularly delivered amygdalin occurs in humans, with most of the intact compound eventually excreted in urine.[26,29]

References:

  1. Gostomski FE: The effects of amygdalin on the Krebs-2 carcinoma and adult and fetal DUB(ICR) mice. [Abstract] Diss Abstr Int B 39 (5): 2075-B, 1978.
  2. Wodinsky I, Swiniarski JK: Antitumor activity of amygdalin MF (NSC-15780) as a single agent and with beta-glucosidase (NSC-128056) on a spectrum of transplantable rodent tumors. Cancer Chemother Rep 59 (5): 939-50, 1975 Sep-Oct.
  3. Laster WR Jr, Schabel FM Jr: Experimental studies of the antitumor activity of amygdalin MF (NSC-15780) alone and in combination with beta-glucosidase (NSC-128056). Cancer Chemother Rep 59 (5): 951-65, 1975 Sep-Oct.
  4. Stock CC, Tarnowski GS, Schmid FA, et al.: Antitumor tests of amygdalin in transplantable animal tumor systems. J Surg Oncol 10 (2): 81-8, 1978.
  5. Menon MM, Bhide SV: Perinatal carcinogenicity of isoniazid (INH) in Swiss mice. J Cancer Res Clin Oncol 105 (3): 258-61, 1983.
  6. Newton GW, Schmidt ES, Lewis JP, et al.: Amygdalin toxicity studies in rats predict chronic cyanide poisoning in humans. West J Med 134 (2): 97-103, 1981.
  7. Hill GJ 2nd, Shine TE, Hill HZ, et al.: Failure of amygdalin to arrest B16 melanoma and BW5147 AKR leukemia. Cancer Res 36 (6): 2102-7, 1976.
  8. Lea MA, Koch MR: Effects of cyanate, thiocyanate, and amygdalin on metabolite uptake in normal and neoplastic tissues of the rat. J Natl Cancer Inst 63 (5): 1279-83, 1979.
  9. Carter JH, McLafferty MA, Goldman P: Role of the gastrointestinal microflora in amygdalin (laetrile)-induced cyanide toxicity. Biochem Pharmacol 29 (3): 301-4, 1980.
  10. Khandekar JD, Edelman H: Studies of amygdalin (laetrile) toxicity in rodents. JAMA 242 (2): 169-71, 1979.
  11. Manner HW, DiSanti SJ, Maggio MI, et al.: Amygdalin, vitamin A and enzyme induced regression of murine mammary adenocarcinomas. J Manipulative Physiol Ther 1 (4): 246-8, 1978.
  12. Ovejera AA, Houchens DP, Barker AD, et al.: Inactivity of DL-amygdalin against human breast and colon tumor xenografts in athymic (nude) mice. Cancer Treat Rep 62 (4): 576-8, 1978.
  13. Lewis JP: Laetrile. West J Med 127 (1): 55-62, 1977.
  14. Schmidt ES, Newton GW, Sanders SM, et al.: Laetrile toxicity studies in dogs. JAMA 239 (10): 943-7, 1978.
  15. Dorr RT, Paxinos J: The current status of laetrile. Ann Intern Med 89 (3): 389-97, 1978.
  16. Levi L, French WN, Bickis IJ, et al.: Laetrile: a study of its physicochemical and biochemical properties. Can Med Assoc J 92 (20): 1057-61, 1965.
  17. Biaglow JE, Durand RE: The enhanced radiation response of an in vitro tumour model by cyanide released from hydrolysed amygdalin. Int J Radiat Biol Relat Stud Phys Chem Med 33 (4): 397-401, 1978.
  18. Bhatti RA, Ablin RJ, Guinan PD: Tumour-associated directed immunity in prostatic cancer: effect of amygdalin. IRCS Med Sci Biochem 9 (1): 19, 1981.
  19. Koeffler HP, Lowe L, Golde DW: Amygdalin (Laetrile): effect on clonogenic cells from human myeloid leukemia cell lines and normal human marrow. Cancer Treat Rep 64 (1): 105-9, 1980.
  20. Syrigos KN, Rowlinson-Busza G, Epenetos AA: In vitro cytotoxicity following specific activation of amygdalin by beta-glucosidase conjugated to a bladder cancer-associated monoclonal antibody. Int J Cancer 78 (6): 712-9, 1998.
  21. Moertel CG, Ames MM, Kovach JS, et al.: A pharmacologic and toxicological study of amygdalin. JAMA 245 (6): 591-4, 1981.
  22. Newmark J, Brady RO, Grimley PM, et al.: Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue. Proc Natl Acad Sci U S A 78 (10): 6513-6, 1981.
  23. Navarro MD: Five years experience with laetrile therapy in advanced cancer. Acta Unio Int Contr Cancrum 15(suppl 1): 209-21, 1959.
  24. Conchie J, Findlay J, Levvy GA: Mammalian glycosidases: distribution in the body. Biochem J 71 (2): 318-25, 1959.
  25. Herbert V: Laetrile: the cult of cyanide. Promoting poison for profit. Am J Clin Nutr 32 (5): 1121-58, 1979.
  26. Ames MM, Moyer TP, Kovach JS, et al.: Pharmacology of amygdalin (laetrile) in cancer patients. Cancer Chemother Pharmacol 6 (1): 51-7, 1981.
  27. Unproven methods of cancer management. Laetrile. CA Cancer J Clin 22 (4): 245-50, 1972 Jul-Aug.
  28. Shils ME, Hermann MG: Unproved dietary claims in the treatment of patients with cancer. Bull N Y Acad Med 58 (3): 323-40, 1982.
  29. Ames MM, Kovach JS, Flora KP: Initial pharmacologic studies of amygdalin (laetrile) in man. Res Commun Chem Pathol Pharmacol 22 (1): 175-85, 1978.

This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http:// cancer .gov or call 1-800-4-CANCER.

WebMD Public Information from the National Cancer Institute

Last Updated: September 04, 2014
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