What mechanisms or conditions could explain the observed and reported cases of anticancer efficacy of Amygdalin _<em>(</em><i>Vitamin B17</i>₎?

<p dir="ltr">or: A didactic application of the hypothesis that the anticancer effect of natural nitrile glycosides results from their hydrolysis, <i>in vivo </i>and/or<i> in vitro</i>, into amide and carboxylic acid derivatives — in a stoichiometric ratio of 4.87:1</p><p>--------</p><p dir="ltr"><a href="https://anti-cancer.eu/" rel="noopener" target="_blank">anticancer activity of glycoside amides .::. timeline of idea development (anti-cancer.eu)</a></p><p>--------</p><p dir="ltr"><b>INTRODUCTION</b></p><p dir="ltr">The apricot is a fruit known to people for millennia (WHAT MAKES ARMENIA SPECIAL?, 2016) (Harutyunyan, 2014). Archaeological excavations in the ancient Armenian city of Shenchovit near Yerevan revealed overlaid apricot excavations dating back to 6,000 years BC. The first written mention of apricot was 4,000 years ago in a letter from a Chinese resident. The well-known apricot comes from a variety of the high-mountainous region of Hindu Kush - Central Asia, where the borders of China, Tajikistan, Afghanistan and Pakistan meet today. Natural forest and very old apricot trees can still be found in northeast China and the Caucasus.</p><p dir="ltr">It is a well-known fact by derontologists that the <i>Hunzi people</i> (Ahmed, 2016) that inhabited the highlands of northern Pakistan, not far from where the apricot originates, are the healthiest and longest-lived people in the world. According to researchers and medical scientists who studied the life of the Huns in their natural environment in the 1950s and 1960s, one hundred percent of them had perfect vision, and cancer, heart attack, high blood pressure, high cholesterol and even appendicitis and gout were unknown states for them.</p><p dir="ltr"><b>BACKGROUND</b></p><p dir="ltr">Throughout the year, their diet was rich in dried fruits and nuts, with apricots and apricot kernels predominating, and their main source of fat was apricot seeds. Apricots were an important part of the Hunzi life.</p><h4>The apricot kernels contain (Femenia, Rossello, Mulet, & Canellas, 1995) an average of 21% protein and 52% vegetable oil and are widely used as a substitute for almonds in the food, cosmetic and pharmaceutical industries. Due to its high content of <i>amygdalin</i>, apricot seeds are a source of <i>Vitamin B17</i> and are used in alternative medicine for cancer therapy.</h4><p dir="ltr">The American Cancer Society notes that apricots, as well as other carotene-rich fruits, reduce the risk of cancer of the larynx, esophagus and lungs.</p><p dir="ltr">This scientific research concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of <i>natural glycoside-nitriles</i> (<i>cyano-glycosides</i>). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semi-empirical methods, are considered.</p><p dir="ltr"><b>OBJECTIVES</b></p><p dir="ltr">Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and/or modified forms to counteract "external" bioactive activity. For their part, cancers have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops accordingly.</p><p dir="ltr">A derived framework that precisely outlines the hydrolytic processes occurring in the bloodstream, the transfer of a specific molecular hydrolytic form to the cancer cell membrane, and—through time-dependent density-functional quantum-chemical modeling—its transmembrane passage and subsequent re-hydrolysis within the cell into bioactive compounds that induce chemical apoptosis, bypassing the cell’s non-genetic regulatory mechanisms that attempt to resist the process.</p><p dir="ltr">Used in oncology it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime).</p><p dir="ltr"><br></p><p dir="ltr"><b>METHODOLOGY AND CONDUCT OF THE RESEARCH</b></p><p dir="ltr">The theoretical foundation and conceptual development are based on the article: “<i>Theoretical Analysis for the Safe Form and Dosage of Amygdalin Product</i>” – DOI: <a href="https://doi.org/10.2174/1871520620666200313163801" target="_blank">10.2174/1871520620666200313163801</a>.</p><p dir="ltr">The delineation of the biochemical cycle governing the transmembrane passage of the active anticancer pharmaceutical form into the cancer cell is based on our original research article: „<i>Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell</i>“ – DOI: <a href="https://doi.org/10.2174/1871520620999201103201008" target="_blank">10.2174/1871520620999201103201008</a>.</p><p dir="ltr">The cellular effects and toxicity profiles of the active pharmaceutical forms are published in „<i>Theoretical Analysis of Anticancer Cellular Effects of Glycoside Amides</i>“ – DOI: <a href="https://doi.org/10.2174/1871520621666210903122831" target="_blank">10.2174/1871520621666210903122831</a>.</p><p dir="ltr">The complete methodological framework is detailed in the monographic work “<i>Theoretical study of anticancer activity of glycoside amides</i>” - DOI: <a href="https://doi.org/10.5281/zenodo.7295357" target="_blank">10.5281/zenodo.7295357</a></p><h3>The study is presented in greater detail, with a more descriptive and applied focus, in the “<i>ATLAS - </i><i>Interpretable prognosis for susceptibility to active anti-cancer molecular forms, based on amides/carboxylic acids - hydrolysis derivatives of natural nitrile glycosides, of transcriptome cell lines inherent in tumors</i>“ - DOI: <a href="https://doi.org/10.5281/zenodo.13777292" target="_blank">10.5281/zenodo.13777292</a></h3><p dir="ltr"><br></p><p dir="ltr"><b>RESULTS</b></p><p dir="ltr">The accumulated knowledge from the <i>Hunza </i>tradition, combined with decades of scientific advancement in synthesis and biochemistry, has made the production of nitrile amides a routine process — particularly through the use of nitrile hydratase. Thus, humanity holds in its hands a huge medicinal resource that can provide treatment for diseases of all parts of conservative medicine.</p><p dir="ltr">The hydrolyzed to amide/carboxylic acid nitrile/cyanide carbohydrates will occupy one of the fundamental steps of countless future clinical practices. This is the purpose of our modest research!</p><p dir="ltr"><br></p><p dir="ltr"><b>CONCLUSIONS</b></p><p dir="ltr"><br></p><ol><li>The amide derivatives of nitrile glycosides are potential chemical compounds with anti-cancer activity;</li><li>the cancer cell seeks to shift the hydrolysis of these derivatives in a direction that would not pass through its cell membrane;</li><li>the amide-carboxylic derivatives of nitrile glycosides can deliver extremely toxic compounds inside the tumor cell itself and thus block and / or permanently damage its normal physiology;</li><li>the use of these compounds in oncology could turn cancer from a lethal to a chronic disease (such as diabetes). The cause and conditions of the disease are not eliminated, but the number of cancer cells could be kept low for a long time (even a lifetime);</li><li>amides resulting from the hydrolysis of nitrile glycosides would be able to cross the cell membrane of a cancer cell and thus cause its cellular response;</li><li>the pharmaceutical form must represent the exact amide/carboxylic acid ratio for the corresponding active anticancer cell form;</li><li>clinical concentrations are more than 7 times higher than those of nitrile glycosides due to their reduced toxicity;</li><li>no significant deviations are observed, on a theoretical level, in the complex use of several pharmaceutical forms together and/or sequentially.</li></ol><p dir="ltr"><br></p><p dir="ltr"><b>RESOURCES</b></p><p dir="ltr">Other glycoside-nitrile homologues that have been reported to have anti-cancer activity are:</p><p dir="ltr"><i>Prunus spp.</i> (Karakas, et al., 2019), <i>Lucuma spp.</i> (Prabhu, Selvam, & Rajeswari, 2018), <i>Vicia spp.</i> (Salehi, et al., 2021), <i>Sambucus spp.</i> (Thole, et al., 2006), <i>Sorghum spp.</i> (Smolensky, et al., 2018), <i>Taxus spp.</i> (Durak, Büber, Devrim, Kocaoğlu, & Durak, 2014), <i>Zieria spp.</i> (Spalding, 1991), <i>Macadamia spp.</i> (Desegaulx, Sirdaarta, Rayan, Cock, & McDonnell, 2015). Glycosides containing α-hydroxynitrile moieties: <i>Nandina spp</i><i>.</i> (Taha, Khalil, & Abubakr, 2020). Glycosides with aliphatic substituents: <i>Linum spp.</i> (Szewczyk, et al., 2014), <i>Trifolium spp.</i> (Sabudak & Guler, 2009), <i>Lotus spp.</i> (Tong, et al., 2020), <i>Maniholt spp.</i> (Veerapagu, Latha, Ramanathan, & Jeya, 2020), <i>Acacia spp.</i> (Sakthivel, Kannan, Angeline, & Guruvayoorappan, 2012), <i>Triglochin spp.</i> (Lellau & Liebezeit, 2003), <i>Deidamia spp.</i> и <i>Tetrapathaea spp.</i> (Yulvianti & Zidorn, 2021), <i>Gynocardia spp.</i> (Kalita, et al., 2018), <i>Pangium spp.</i> (Chye & Sim, 2009) and others.</p><p dir="ltr">These plants are an integral part of Chinese, Caucasian, Altaic, Tibetan, Indonesian, African, Indian, Polynesian, South and Central American folk medicine. They all contain the corresponding nitrile-glycside and calculations show us that they are all homologous in the order of anti-cancer amide/carboxylic derivatives. The action of each is unique and "attacks" individual cancer cell lines, and at times unique ones.</p><p dir="ltr"><br></p><p dir="ltr"><b>APPLYING THE RESULTS</b></p><p dir="ltr">The results of the analysis show that the studied molecular forms do NOT contradict conservative oncology. Their activity is significant and many times exceeds a number of approved products for treatment.</p><h3>Anti-cancer agents could best be administered orally. Their toxicity is many times less than that of most references accepted in clinical chemotherapy – <i>p.127</i> of DOI: <a href="https://doi.org/10.5281/zenodo.13777292" target="_blank">10.5281/zenodo.13777292</a></h3><p dir="ltr"><br></p><p dir="ltr"><b>CLINICAL CONTROL</b></p><p dir="ltr">Amygdalin, in its pure vitamin-like form, is HIGHLY TOXIC to animal organisms when administered at clinical doses. It is only considered safe at extremely low concentrations and for very short durations. Its spontaneous conversion into a pharmaceutical agent, whether <i>in vivo </i>and/or <i>in vitro</i>, follows probabilistic patterns governed by statistical laws and lacks the reproducibility required by conventional medicine.</p><h3>!!! It is imperative to thoroughly read the section titled 'Clinical Control’ – <i>p.135</i> of DOI: <a href="https://doi.org/10.5281/zenodo.13777292" target="_blank">10.5281/zenodo.13777292</a> !!!</h3><h3>---</h3><p dir="ltr"><a href="https://anti-cancer.eu/" rel="noopener" target="_blank">anticancer activity of glycoside amides .::. timeline of idea development (anti-cancer.eu)</a></p>