Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Mini-Review Article

The Postulated Mechanism of Action of Amygdalin (Vitamin B17) on Cancer Cells

Author(s): Mohamed Ali El-Desouky, Abdelgawad Ali Fahmi* and Karima Mahmoud Nasraldin

Volume 23, Issue 8, 2023

Published on: 26 December, 2022

Page: [894 - 899] Pages: 6

DOI: 10.2174/1871520623666221124143751

Price: $65

conference banner
Abstract

The current study demonstrates amygdalin’s (vitamin B17) postulated mechanism of action on cancer cells where it kills cells by selective toxicity, promotes apoptosis via cell cycle arrest, induces apoptosis via intrinsic cell death pathway (the mitochondria-initiated pathway), and enhances immunity. Thus, amygdalin can be considered a valuable natural cancer therapeutic agent. The toxicity of Amygdalin was reviewed. Moreover, solutions to avoid the cyanide poisoning have been proposed.

Keywords: Amygdalin, vitamin B17, mechanism, caspase3, cytochrome c oxidase, p53.

Graphical Abstract
[1]
Sharma, R.; Kr Sharma, H. A review on plants having anti-cancer activity. Pharm. Res., 2017, 4(2), 39-62.
[2]
Salama, R.H.; Ramadan, A.E.R.G.; Alsanory, T.A.; Herdan, M.O.; Fathallah, O.M.; Alsanory, A.A. Experimental and therapeutic trials of amygdalin. Inter. J. Biochem. Pharmacol., 2019, 1(1), 21-26.
[http://dx.doi.org/10.18689/ijbp-1000105]
[3]
Amirah, A. Preventive role of amygdalin in squamous cell carcinoma induced in hamsters. Int. J. Pharm. Sci. Med., 2017, 2, 8-14.
[4]
Ioannis, P.; Anastasis, S.; Andreas, Y. Tripterygium wilfordii Extract (Triptolide) and amygdalin promotes cell death in cancer cells: True or a myth. Am. J. Cancer Prev., 2015, 3(4), 77-83.
[http://dx.doi.org/10.12691/ajcp-3-4-3]
[5]
El-Desouky, M.A.; Fahmi, A.A.; Abdelkader, I.Y.; Nasraldin, K.M. Anticancer effect of amygdalin (Vitamin B-17) on hepatocellular carcinoma cell line (HepG2) in the presence and absence of zinc. Anticancer. Agents Med. Chem., 2020, 20(4), 486-494.
[http://dx.doi.org/10.2174/1871520620666200120095525] [PMID: 31958042]
[6]
Hye Min, L.; Moon, A. Amygdalin regulates apoptosis and adhesion in Hs578T triple-negative breast cancer cells. Korean Soc. Appl. Pharmacol., 2016, 24(1), 62-66.
[7]
Mosadegh, M.S.; Safavi, M.; Rostami, S.; Nadali, F.; Shams, A.M.R. Apoptosis induction of armeniacae semen extractin human acute leukemia (NALM-6 and KG-1) cells. Int. J. Hematol. stem cell Res., 2019, 13(3), 116-121.
[8]
Xu, X.; Song, Z. Advanced research on anti-tumor effects of amygdalin. J. Cancer Res. Ther., 2014, 10(5)(Suppl. 1), 3-7.
[http://dx.doi.org/10.4103/0973-1482.139743] [PMID: 25207888]
[9]
Makarević, J.; Rutz, J.; Juengel, E.; Kaulfuss, S.; Reiter, M.; Tsaur, I.; Bartsch, G.; Haferkamp, A.; Blaheta, R.A. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2. PLoS One, 2014, 9(8)e105590
[http://dx.doi.org/10.1371/journal.pone.0105590] [PMID: 25136960]
[10]
He, X.Y.; Wu, L.J.; Wang, W.X.; Xie, P.J.; Chen, Y.H.; Wang, F. Amygdalin-A pharmacological and toxicological review. J. Ethnopharmacol., 2020, 23(254)112717
[http://dx.doi.org/10.1016/j.jep.2020.112717]
[11]
Guo, J.; Wu, W.; Sheng, M.; Yang, S.; Tan, J. Amygdalin inhibits renal fibrosis in chronic kidney disease. Mol. Med. Rep., 2013, 7(5), 1453-1457.
[http://dx.doi.org/10.3892/mmr.2013.1391] [PMID: 23525378]
[12]
Pommier, P.; Gomez, F.; Sunyach, M.P.; D’Hombres, A.; Carrie, C.; Montbarbon, X. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J. Clin. Oncol., 2004, 22(8), 1447-1453.
[http://dx.doi.org/10.1200/JCO.2004.07.063] [PMID: 15084618]
[13]
Relman, A.S. Closing the books on Laetrile. N. Engl. J. Med., 1982, 306(4), 236-236.
[http://dx.doi.org/10.1056/NEJM198201283060410] [PMID: 7054687]
[14]
Dorris, J. Hutchison Schmid, F. A. OBITUARIES-Kanematsu Sugiura 1890-1979. Cancer Res., 1980, 40, 2625-2626.
[15]
Fukuda, T.; Ito, H.; Mukainaka, T.; Tokuda, H.; Nishino, H.; Yoshida, T. Anti-tumor promoting effect of glycosides from Prunus persica seeds. Biol. Pharm. Bull., 2003, 26(2), 271-273.
[http://dx.doi.org/10.1248/bpb.26.271] [PMID: 12576693]
[16]
Yan, J.; Tong, S.; Li, J.; Lou, J. Preparative isolation and purification of amygdalin from Prunus armeniaca L. with high recovery by high‐speed countercurrent chromatography. J. Liq. Chromatogr. Relat. Technol., 2006, 29(9), 1271-1279.
[http://dx.doi.org/10.1080/10826070600598985]
[17]
Zhou, C.; Qian, L.; Ma, H.; Yu, X.; Zhang, Y.; Qu, W.; Zhang, X.; Xia, W. Enhancement of amygdalin activated with β-d-glucosidase on HepG2 cells proliferation and apoptosis. Carbohydr. Polym., 2012, 90(1), 516-523.
[http://dx.doi.org/10.1016/j.carbpol.2012.05.073] [PMID: 24751072]
[18]
Zbynovská, K.; Halenár, M.; Chrastinová, L.; Ondruška, L.; Jurcík, R.; Cupka, P.; Tušimová, E.; Kovácik, A.; Kolesár, E.; Valuch, J. Oral and intramuscular application of cyanogenic glycoside amygdalin did not induce changes in haematological profile of male rabbits. Potravin. Slovak J. Food Sci., 2017, 11(1), 315-321.
[http://dx.doi.org/10.5219/756]
[19]
Chang, L.W.; Zhu, H.P.; Li, W.B.; Liu, H.C.; Zhang, Q.S.; Chen, H.B. Protective effects of amygdalin on hyperoxia-exposed type II alveolar epithelial cells isolated from premature rat lungs in vitro. Zhonghua Er Ke Za Zhi, 2005, 43(2), 118-123.
[PMID: 15833168]
[20]
Do, J.S.; Hwang, J.K.; Seo, H.J.; Woo, W.H.; Nam, S.Y. Antiasthmatic activity and selective inhibition of type 2 helper T cell response by aqueous extract of semen armeniacae amarum. Immunopharmacol. Immunotoxicol., 2006, 28(2), 213-225.
[http://dx.doi.org/10.1080/08923970600815253] [PMID: 16873091]
[21]
Wei, Y.; Xie, Q.; Ito, Y. Preparative separation of axifolin-3-glucoside, hyperoside and amygdalin from plant extracts by high speed countercurrent chromatography. J. Liq. Chromatogr. Relat. Technol., 2009, 32(7), 1010-1022.
[http://dx.doi.org/10.1080/10826070902790983] [PMID: 20046896]
[22]
Shim, S.M.; Kwon, H. Metabolites of amygdalin under simulated human digestive fluids. Int. J. Food Sci. Nutr., 2010, 61(8), 770-779.
[http://dx.doi.org/10.3109/09637481003796314] [PMID: 20528582]
[23]
Moertel, C.G.; Fleming, T.R.; Rubin, J.; Kvols, L.K.; Sarna, G.; Koch, R.; Currie, V.E.; Young, C.W.; Jones, S.E.; Davignon, J.P. A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. N. Engl. J. Med., 1982, 306(4), 201-206.
[http://dx.doi.org/10.1056/NEJM198201283060403] [PMID: 7033783]
[24]
Newmark, J.; Brady, R. O.; Grimley, P. M.; Gal, A. E.; Waller, S. G.; Thistlethwaite, J. R. Amygdalin (Laetrile) and prunasin β- glucosidases: Distribution in germ-free rat and in human tumor tissue. Proc. Natl. Acad. Sci. U. S. A., 1981, 78(101), 6513-6516.
[http://dx.doi.org/10.1073/pnas.78.10.6513]
[25]
Manhardt, M.A. Correlation of injected amygdalin and urinary thiocyanate in JAX C57 BL/KsJ mice. Master’s Thesis, Loyola University, Chicago, 1981.
[26]
Ge, B.Y.; Chen, H.X.; Han, F.M.; Chen, Y. Identification of amygdalin and its major metabolites in rat urine by LC-MS/MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2007, 857(2), 281-286.
[http://dx.doi.org/10.1016/j.jchromb.2007.07.036] [PMID: 17720632]
[27]
Makarević, J.; Rutz, J.; Juengel, E.; Kaulfuss, S.; Tsaur, I.; Nelson, K.; Pfitzenmaier, J.; Haferkamp, A.; Blaheta, R.A. Amygdalin influences bladder cancer cell adhesion and invasion in vitro. PLoS One, 2014, 9(10)e110244
[http://dx.doi.org/10.1371/journal.pone.0110244] [PMID: 25333694]
[28]
Brenner, G.R.; Brenner, M.; Mahon, S.B.; Lee, J.; Kim, J.; Mukai, D.; Goodman, S.; Kreuter, K.A.; Ahdout, R.; Mohammad, O.; Sharma, V.S. Comparison of cobinamide to hydroxocobalamin in reversing cyanide physiologic effects in rabbits using diffuse optical spectroscopy monitoring. J. Biomed. Opt., 2010, 15(1)017001
[http://dx.doi.org/10.1117/1.3290816]
[29]
Nůsková, H.; Vrbacký, M.; Drahota, Z.; Houštěk, J. Cyanide inhibition and pyruvate-induced recovery of cytochrome c oxidase. J. Bioenerg. Biomembr., 2010, 42(5), 395-403.
[http://dx.doi.org/10.1007/s10863-010-9307-6] [PMID: 20725851]
[30]
Thompson, J.P.; Marrs, T.C. Hydroxocobalamin in cyanide poisoning. Clin. Toxicol. (Phila.), 2012, 50(10), 875-885.
[http://dx.doi.org/10.3109/15563650.2012.742197] [PMID: 23163594]
[31]
Forsyth, J.C.; Mueller, P.D.; Becker, C.E.; Osterloh, J.; Benowitz, N.L.; Rumack, B.H.; Hall, A.H. Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers. J. Toxicol. Clin. Toxicol., 1993, 31(2), 277-294.
[http://dx.doi.org/10.3109/15563659309000395] [PMID: 8492341]
[32]
Oyewole, O.I.; Olayinka, E.T. Hydroxocobalamin (Vit b 12a) effectively reduced extent of cyanide poisoning arising from oral amygdalin ingestion in rats. J. Toxicol. Environ. Heal. Sci., 2009, 1(1), 8-11.
[33]
Enculescu, M. Vitamin B 17/Laetrile/Amygdalin (a review). Bull. Univ. Agric. Sci. Vet. Med. Cluj-Napoca Anim. Sci. Biotechnol., 2009, 66(11), 20-25.
[34]
Hariharakrishnan, J.; Anand, T.; Satpute, R.M.; Jayaraj, R.; Prasad, G.B.K.S.; Bhattacharya, R. Activity and gene expression profile of certain antioxidant enzymes in different organs of rats after subacute cyanide exposure: Effect of alpha-ketoglutarate. Drug Chem. Toxicol., 2009, 32(3), 268-276.
[http://dx.doi.org/10.1080/01480540902882218] [PMID: 19538024]
[35]
Shragg, T.A.; Albertson, T.E.; Fisher, C.J. Cyanide poisoning after bitter almond ingestion. West. J. Med., 1982, 136(1), 65-69.
[PMID: 7072244]
[36]
Michlmayr, H.; Kneifel, W. β-Glucosidase activities of lactic acid bacteria: mechanisms, impact on fermented food and human health. FEMS Microbiol. Lett., 2014, 352(1), 1-10.
[http://dx.doi.org/10.1111/1574-6968.12348] [PMID: 24330034]
[37]
Mégarbane, B.; Delahaye, A.; Goldgran-Tolédano, D.; Baud, F.J. Antidotal treatment of cyanide poisoning. J. Chin. Med. Assoc., 2003, 66(4), 193-203.
[PMID: 12854870]
[38]
Jaswal, V.; Palanivelu, J.; Ramalingam, C. Effects of the Gut microbiota on Amygdalin and its use as an anti-cancer therapy: Substantial review on the key components involved in altering dose efficacy and toxicity. Biochem. Biophys. Rep., 2018, 14, 125-132.
[http://dx.doi.org/10.1016/j.bbrep.2018.04.008] [PMID: 29872744]
[39]
Moon, J-Y.; Kim, S-W.; Yun, G-M.; Lee, H-S.; Kim, Y-D.; Jeong, G-J.; Ullah, I.; Rho, G-J.; Jeon, B-G. Inhibition of cell growth and down-regulation of telomerase activity by amygdalin in human cancer cell lines. Anim. Cells Syst., 2015, 19(5), 295-304.
[http://dx.doi.org/10.1080/19768354.2015.1060261]
[40]
Ahmed, A.; Tollefsbol, T.O. Telomerase, telomerase inhibition, and cancer. J. Anti Aging Med., 2003, 6(4), 315-325.
[http://dx.doi.org/10.1089/109454503323028911] [PMID: 15142433]
[41]
Zheng, X.; Wang, X.; Mao, H.; Wu, W.; Liu, B.; Jiang, X. Hypoxia-specific ultrasensitive detection of tumours and cancer cells in vivo. Nat. Commun., 2015, 6(1), 5834.
[http://dx.doi.org/10.1038/ncomms6834] [PMID: 25556360]
[42]
Iib, S.; Values, B. A. T. Benzaldehyde 1984.
[43]
Alwan, A.M.; Afshari, J.T. In vivo growth inhibition of human caucasian prostate adenocarcinoma in nude mice induced by amygdalin with metabolic enzyme combinations. BioMed Res. Int., 2022, 2022(21), 1-7.
[http://dx.doi.org/10.1155/2022/4767621] [PMID: 35637752]
[44]
Rowe, A.V. The non-teratogenic effects in mice progeny by maternal treatment with amygdalin recommended citation. Master’s Thesis, Loyola University, Chicago, 1978.
[45]
Nacci, G. Thousand plants against cancer without Chemotherapy, 2008. Available from: https://www.pieronuciari.it/wp/wp-content/uploads/2021/03/Thousand-Plants-against-Cancer-without-Chemo-20101.pdf
[46]
Heinrich, M. CRC Handbook of Medicinal Spices. J. Ethnopharmacol., 2003, 2(88), 299.
[http://dx.doi.org/10.1016/S0378-8741(03)00214-9]
[47]
Shalayel, M.H.F. Beyond laetrile (Vitamin B-17) controversy-antitumor illusion or revolution. Br. Biomed. Bull., 2017, 5(1), 296.
[48]
The Cancer Group Institute, In: Complementary and Natural Treatments for Bladder Cancer It’s Your Life, Live It!; Beverly Hills: California, 2011, 328.
[49]
Green, D.R.; Kroemer, G. Cytoplasmic functions of the tumour suppressor p53. Nature, 2009, 458(7242), 1127-1130.
[http://dx.doi.org/10.1038/nature07986] [PMID: 19407794]
[50]
Park, H-J.; Yoon, S-H.; Han, L-S.; Zheng, L-T.; Jung, K-H.; Uhm, Y-K.; Lee, J-H.; Jeong, J-S.; Joo, W-S.; Yim, S-V.; Chung, J.H.; Hong, S.P. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells. World J. Gastroenterol., 2005, 11(33), 5156-5161.
[http://dx.doi.org/10.3748/WJG.V11.I33.5156] [PMID: 16127745]
[51]
Journal, I.; Sciences, M.; Palack, B.A. Effect of amygdalin in the treatment of squamous cell carcinoma induced in the buccal pouch of golden Syrian hamster. IOSR J. Dent. Med. Sci., 2016, 15(2), 75-79.
[http://dx.doi.org/10.9790/0853-15297579]
[52]
Cheah, P-L.; Frcpath, M. p53: An overview of over two decades of study. Malays. J. Pathol., 2001, 23(1), 9-16.
[53]
Juengel, E.; Thomas, A.; Rutz, J.; Makarevic, J.; Tsaur, I.; Nelson, K.; Haferkamp, A.; Blaheta, R.A. Amygdalin inhibits the growth of renal cell carcinoma cells in vitro. Int. J. Mol. Med., 2016, 37(2), 526-532.
[http://dx.doi.org/10.3892/ijmm.2015.2439] [PMID: 26709398]
[54]
Nakano, K.; Vousden, K.H. PUMA, a novel proapoptotic gene, is induced by p53. Mol. Cell, 2001, 7(3), 683-694.
[http://dx.doi.org/10.1016/S1097-2765(01)00214-3] [PMID: 11463392]
[55]
Chipuk, J.E.; Fisher, J.C.; Dillon, C.P.; Kriwacki, R.W.; Kuwana, T.; Green, D.R. Mechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins. Proc. Natl. Acad. Sci. USA, 2008, 105(51), 20327-20332.
[http://dx.doi.org/10.1073/pnas.0808036105] [PMID: 19074266]
[56]
Park, J.H.; Zhuang, J.; Li, J.; Hwang, P.M. p53 as guardian of the mitochondrial genome. FEBS Lett., 2016, 590(7), 924-934.
[http://dx.doi.org/10.1002/1873-3468.12061] [PMID: 26780878]
[57]
Shoshan-Barmatz, V.; Ben-Hail, D.; Admoni, L.; Krelin, Y.; Tripathi, S.S. The mitochondrial voltage-dependent anion channel 1 in tumor cells. Biochim. Biophys. Acta Biomembr., 2015, 1848(10), 2547-2575.
[http://dx.doi.org/10.1016/j.bbamem.2014.10.040] [PMID: 25448878]
[58]
Robles, A.I.; Bemmels, N.A.; Foraker, A.B.; Harris, C.C. APAF-1 is a transcriptional target of p53 in dna damage-induced apoptosis. Cancer Res., 2001, 61(18), 6660-6664.
[59]
Elmore, S. Apoptosis: a review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[60]
Baroni, A.; Paoletti, I.; Greco, R.; Satriano, R.A.; Ruocco, E.; Tufano, M.A.; Perez, J.J. Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells. Exp. Dermatol., 2005, 14(11), 854-859.
[http://dx.doi.org/10.1111/j.1600-0625.2005.00368.x] [PMID: 16232308]
[61]
Qadir, M.; Fatima, K. Review on pharmacological activity of amygdalin. Arch. Cancer Res., 2017, 5(4), 160.
[http://dx.doi.org/10.21767/2254-6081.100160]
[62]
Nelson, L. Acute cyanide toxicity: Mechanisms and manifestations. J. Emerg. Nurs., 2006, 32(4)(Suppl.), S8-S11.
[http://dx.doi.org/10.1016/j.jen.2006.05.012] [PMID: 16860675]
[63]
Cho, A-Y.; Shin, K-J.; Chung, J.; Oh, S. A sensitive enzyme immunoassay for amygdalin in food extracts using a recombinant antibody. J. Food Prot., 2008, 71(10), 2048-2052.
[http://dx.doi.org/10.4315/0362-028X-71.10.2048]
[64]
Soto-Blanco, B.; Górniak, S.L. Milk transfer of cyanide and thiocyanate: Cyanide exposure by lactation in goats. Vet. Res., 2003, 34(2), 213-220.
[http://dx.doi.org/10.1051/vetres:2002068] [PMID: 12657213]
[65]
Silva, M.C.P.; Terra, W.R.; Ferreira, C. Absorption of toxic β-glucosides produced by plants and their effect on tissue trehalases from insects. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 2006, 143(3), 367-373.
[http://dx.doi.org/10.1016/j.cbpb.2005.12.011] [PMID: 16458033]
[66]
Chen, J.; Yan, X.; Kim, T.J.; Kim, S.H.; Kim, K.T.; Lee, Y.K.; Cho, C.W.; Baek, J.S.; Park, Y.K.; Kim, Y.H.; Lee, W-J.; Kang, J-S. Metabolic pharmacokinetics in rats: Differences between pure amygdalin and amygdalin in a decoction of peach seeds. Bull. Korean Chem. Soc., 2012, 33(5), 1470-1474.
[http://dx.doi.org/10.5012/bkcs.2012.33.5.1470]
[67]
Bromley, J.; Hughes, B.G.M.; Leong, D.C.S.; Buckley, N.A. Life-threatening interaction between complementary medicines: Cyanide toxicity following ingestion of amygdalin and vitamin C. Ann. Pharmacother., 2005, 39(9), 1566-1569.
[http://dx.doi.org/10.1345/aph.1E634] [PMID: 16014371]
[68]
Calabrese, E.J. Possible adverse side effects from treatment with laetrile. Med. Hypotheses, 1979, 5(9), 1045-1049.
[http://dx.doi.org/10.1016/0306-9877(79)90053-7] [PMID: 522706]
[69]
Chang, H.K.; Shin, M.S.; Yang, H.Y.; Lee, J.W.; Kim, Y.S.; Lee, M.H.; Kim, J.; Kim, K.H.; Kim, C.J. Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells. Biol. Pharm. Bull., 2006, 29(8), 1597-1602.
[http://dx.doi.org/10.1248/bpb.29.1597] [PMID: 16880611]
[70]
Milazzo, S.; Ernst, E.; Lejeune, S.; Boehm, K.; Horneber, M. In: Laetrile treatment for cancer (review). Ed. Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Group, 2011.
[http://dx.doi.org/10.1002/14651858.CD005476.pub3]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy