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Current Pharmaceutical Biotechnology 2021Amygdalin has anticancer benefits because of its active component, hydrocyanic acid. However, the underlying molecular mechanism is unclear.
BACKGROUND
Amygdalin has anticancer benefits because of its active component, hydrocyanic acid. However, the underlying molecular mechanism is unclear.
OBJECTIVE
This study aimed to investigate the molecular mechanism by which amygdalin exerts antiproliferative effects in the human Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line.
METHODS
MCF-7 cells were exposed to amygdalin at a particular IC value for 24 and 48 hours and compared to non-treated cells. An Affymetrix whole-transcript expression array was used to analyze the expression of 32 genes related to DNA replication.
RESULTS
Among the 32 genes, amygdalin downregulated the expression of 16 genes and 19 genes by >1.5-fold at 24 and 48 hours, respectively. At 24 hours, the downregulated genes from the DNA polymerase α-primase complex were POLA1, POLA2, PRIM1, and PRIM2; DNA polymerase δ complex: POLD3; DNA polymerase ε complex: POLE4, Minichromosome Maintenance protein (MCM) complex (helicase): MCM2, MCM3, MCM4, MCM6, and MCM7; clamp and clamp loader: PCNA; nuclease: FEN1; and DNA ligase: LIG1. At 48 hours, the downregulated genes from the DNA polymerase α-primase complex were POLA1, POLA2, and PRIM1; DNA polymerase δ complex: POLD3; DNA polymerase ε complex: POLE and POLE2; MCM complex (helicase): MCM2, MCM3, MCM4, MCM5, MCM6, and MCM7; clamp and clamp loader: PCNA, RFC2, and RFC3; RNase H: RNASEH2A; nucleases: DNA2 and FEN1; and DNA ligase: LIG1.
CONCLUSION
Amygdalin treatment caused downregulation of several genes that play critical roles in DNA replication in the MCF-7 cell line. Thus, it might be useful as an anticancer agent.
Topics: Amygdalin; Breast Neoplasms; Cell Cycle Proteins; DNA Primase; DNA Replication; Female; Humans; Minichromosome Maintenance Complex Component 6
PubMed: 33535947
DOI: 10.2174/1389201022666210203123803 -
Anti-cancer Agents in Medicinal... 2022This article is a continuation of Theoretical Analysis for the Safe Form and Dosage of Amygdalin Product and Theoretical Study of the Process of Passage of Glycoside...
BACKGROUND
This article is a continuation of Theoretical Analysis for the Safe Form and Dosage of Amygdalin Product and Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell. They consider some possible natural modifications and hypothesize that it is not nitrile glycosides that have antitumor properties but their amide / carboxyl derivatives. The possibility of using this circumstance in conservative oncology is also considered. A mechanism for crossing the cell membrane and overcoming the immune functions of the cancer cell is presented. The physiologically active cancer cell itself is quite inert to external influences. It is far more stable than any physiologically active structural and/or functional organismal cell. Its defenses are discussed in detail in the article, and its main weakness was defined, namely: the cancer cell feeds mainly on carbohydrates and/ or carbohydrate complexes. In an effort to preserve its gene set, it has evolved to counteract biologically active substances by maximally preventing its passage through its cell membrane. It is this property that could be used to minimize its effect on the whole body. In the same article, based on theoretical calculations and literature references, a hypothesis is stated: cancers could turn from severe infectious to controlled chronic ones (similar to diabetes, chronic hepatitis, etc.) Objective: The pharmaceutical form allows deviation from the chemically pure substance. It is a convenient and at the same time accessible (from a financial and/or technological point of view) form for admission by patients. Due to the great variety of natural glycosamide nitriles (starting material for the production of amide/ carboxylic acid), modern pharmacology allows their combined intake by chemical nature and concentration of the active form crossing the cell membrane. Natural nitrile glycosides hydrolyzed to amide/carboxylic acid are still unexplored but with great theoretical potential. As biologically active substances, these compounds also have significant toxicity. One of the purposes of this article is to organize laboratory tests on animals.
METHODS
A comparative analysis is performed on the basis of stoichiometric calculations for the concentration of the active form and the prediction of the bioactivity. For this purpose, the following methodology is applied: Data analysis for active anticancer cell molecular form and Determination of the drug dose. The derived chemicals obtained immediately after the passage of glycosamide across the cancer cell membrane are: (R)-2-hydroxy-2-phenylacetamide, (R)-2- hydroxy-2-(4-hydroxyphenyl)acetamide, (R)-2-hydroxy-2-(3-hydroxyphenyl)acetamide, 2-hydroxy-2-methylpropanamide, (S)-2-hydroxy-2-methylbutanamide, 2-hydroxy-3-methylbut-2-enamide, (2Z,4E)-4-(2-amino-1-hydroxy-2-oxoethylide ne)hex-2-enedioic acid, (S)-1-hydroxycyclopent-2-ene-1-carboxamide, (1S,4S)-1,4-dihydroxycyclopent-2-ene-1-carbox amide, (1R,4R)-1,4,5-trihydroxycyclopent-2-ene-1-carboxamide, (Z)-2-((4S,6R)-4,6-dihydroxycyclohex-2-en-1-ylidene) acetamide, (R)-2-hydroxy-3-methylbutanamide, (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide, (Z)-2-((4R,5R,6S)-5,6-dihydroxy-4-methoxycyclohex-2-en-1-ylidene)acetamide, (E)-2-((4R,6S)-4,6-dihydroxycyclohex- 2-en-1-ylidene)acetamide и (E)-2-((4S,5R,6R)-4,5,6-trihydroxycyclohex-2-en-1-ylidene)acetamide.
RESULTS
The use of two or more pharmaceutical forms would not prevent their penetration, subject to the mass ratios between the active antitumor amide and the active carboxyl transfer form.
CONCLUSION
Amides resulting from the hydrolysis of nitrile glycosides would have the ability to cross the cell membrane of a cancer cell and thus cause its cellular response. The pharmaceutical form must represent the exact amide / carboxylic acid ratio for the corresponding active anticancer cell form.
Topics: Amides; Amygdalin; Animals; Carboxylic Acids; Glycosides; Humans; Neoplasms; Pharmaceutical Preparations
PubMed: 34477528
DOI: 10.2174/1871520621666210903122831 -
Molecular Biology Reports Sep 2020Amygdalin induces apoptotic death in several carcinoma cells. Affibody is an engineered protein with a high affinity for human epidermal receptor 2 (HER2). We assessed...
Amygdalin induces apoptotic death in several carcinoma cells. Affibody is an engineered protein with a high affinity for human epidermal receptor 2 (HER2). We assessed the cytotoxic effects of the amygdalin-Z affibody conjugate on two breast carcinoma cell lines. The Z affibody gene was synthesized and transferred into E. coli BL21 as an expression host. After purification, the Z affibody was conjugated to amygdalin. The cytotoxic effects of amygdalin and its Z affibody conjugate on the SK-BR-3, with overexpression of HER2, and MCF-7 cells were evaluated by MTT assay. The effects of amygdalin and its conjugate on apoptotic death and expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were measured. Amygdalin individually showed a potent cytotoxic effect against both MCF-7 (IC = 14.2 mg ml) and SK-BR-3 cells (IC = 13.7 mg ml). However, the amygdalin-Z affibody conjugate had a more cytotoxic effect on SK-BR-3 (IC = 8.27 mg ml) than MCF-7 cells (IC = 19.8 mg ml). Amygdalin had a significant apoptotic effect on both cell lines and the effect of its conjugate on SK-BR-3 cells was significantly more potent than MCF-7 cells. Amygdalin increased Bax and decreased Bcl-2 expression in both cell lines. However, the effect of its conjugate on the Bax and Bcl-2 expression in SK-BR-3 was more potent than MCF-7 cells. In conclusion, the amygdalin-Z affibody conjugate may be considered as a valuable candidate for specific treatment of breast cancer patients with overexpression of HER2. However, further in vivo studies are required to explain the antitumoral effects of constructed amygdalin-Z affibody conjugate.
Topics: Amygdalin; Antineoplastic Agents, Immunological; Breast Neoplasms; Drug Delivery Systems; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoconjugates; MCF-7 Cells; Receptor, ErbB-2; Single-Chain Antibodies
PubMed: 32929653
DOI: 10.1007/s11033-020-05782-z -
International Journal of Biological... Jun 2020Amygdalin, despite possessing anticancerous properties, has been viewed as a controversial choice due to the presence of the cyanide group. Here, we synthesise and...
Amygdalin, despite possessing anticancerous properties, has been viewed as a controversial choice due to the presence of the cyanide group. Here, we synthesise and investigate the potential of alginate-chitosan nanoparticles (ACNPs) as drug delivery agents for amygdalin encapsulation and its delivery to cancer cells. Amygdalin loaded ACNPs were made with both anionic and cationic outer layer to further investigate charge dependency on drug delivery and cytotoxicity. ACNPs encapsulating amygdalin were monodisperse, colloidally stable with ~90% drug encapsulation efficiency and were entirely made from natural materials. The nanoparticles exhibited sustained drug release for a duration of 10 h and significant swelling rates in neutral and slightly acidic environments. The ACNPs successfully adhered to porcine mucin type II when assessed for its mucoadhesion and shown to transmigrate with an average velocity of 1.68 μm/s in uncoated channels, under biomimicked flow conditions. To investigate charge dependency on drug delivery and cytotoxicity, amygdalin loaded ACNPs were made with both anionic and cationic outer layer and assessed. ACNPs demonstrated greater yet sustained anti-cancerous effect on H1299 cell lines in a dose-dependent manner than free amygdalin suggesting greater cellular uptake of the former. In conclusion, biocompatible and biodegradable alginate-chitosan nanoparticles can be used as an effective drug delivery system for sustained and controlled amygdalin release with its improved cytotoxic effect on cancerous cells while protecting normal cells and tissues.
Topics: Amygdalin; Antineoplastic Agents; Cell Line, Tumor; Chitosan; Drug Carriers; Drug Screening Assays, Antitumor; Humans; Lung Neoplasms; Materials Testing; Nanoparticles
PubMed: 32097740
DOI: 10.1016/j.ijbiomac.2020.02.191 -
Plants (Basel, Switzerland) Jul 2022L. (Rosaceae)-syn. (L.) Dumort., (L.) Huth, Lam is commonly known as the apricot tree. The plant is thought to originate from the northern, north-western, and... (Review)
Review
L. (Rosaceae)-syn. (L.) Dumort., (L.) Huth, Lam is commonly known as the apricot tree. The plant is thought to originate from the northern, north-western, and north-eastern provinces of China, although some data show that it may also come from Korea or Japan. The apricot fruit is used medicinally to treat a variety of ailments, including use as an antipyretic, antiseptic, anti-inflammatory, emetic, and ophthalmic remedy. The Chinese and Korean pharmacopeias describe the apricot seed as an herbal medicinal product. Various parts of the apricot plant are used worldwide for their anticancer properties, either as a primary remedy in traditional medicine or as a complementary or alternative medicine. The purpose of this review was to provide comprehensive and up-to-date information on ethnobotanical data, bioactive phytochemicals, anticancer potential, pharmacological applications, and toxicology of the genus , thus providing new perspectives on future research directions. Included data were obtained from online databases such as PubMed/Medline, Google Scholar, Science direct, and Wiley Online Library. Multiple anticancer mechanisms have been identified in in vitro and in vivo studies, the most important mechanisms being apoptosis, antiproliferation, and cytotoxicity. The anticancer properties are probably mediated by the contained bioactive compounds, which can activate various anticancer mechanisms and signaling pathways such as tumor suppressor proteins that reduce the proliferation of tumor cells. Other pharmacological properties resulting from the analysis of experimental studies include neuroprotective, cardioprotective, antioxidant, immunostimulatory, antihyperlipidemic, antibacterial, and antifungal effects. In addition, data were provided on the toxicity of amygdalin, a compound found in apricot kernel seeds, which limits the long-term use of complementary/alternative products derived from . This updated review showed that bioactive compounds derived from are promising compounds for future research due to their important pharmacological properties, especially anticancer. A detailed analysis of the chemical structure of these compounds and their cytotoxicity should be carried out in future research. In addition, translational pharmacological studies are required for the correct determination of pharmacologically active doses in humans.
PubMed: 35890519
DOI: 10.3390/plants11141885 -
Biomolecules Oct 2020Amygdalin is a natural cyanogenic compound that plants produce in the fight against insects and herbivores. Excessive amounts of amygdalin by animals and humans can...
Amygdalin is a natural cyanogenic compound that plants produce in the fight against insects and herbivores. Excessive amounts of amygdalin by animals and humans can potentially lead to fatal intoxication. However, studies confirm that amygdalin has antitumor properties, including the ability to inhibit the proliferation of cancer cells and to induce their apoptosis. The analysis of amygdalin in various matrices is an important analytical problem today. The publication presents the methodology of direct determination of amygdalin in water, sewage, and biological materials using electrospray ionization mass spectrometry (ESI-MS) and a new analytical method using flowing atmospheric-pressure afterglow mass spectrometry (FAPA-MS). The methods of analyte pre-concentration using a magnetic, molecularly imprinted polymer (mag-MIP) and the influence of interferents on the recorded spectra were discussed. Analytical parameters in ESI-MS and FAPA-MS methods were established. The linearity range was 4.5 µg L-45 mg L in positive mode ESI-MS and FAPA-MS. The limit of detection (LOD) for ESI-MS was 0.101 ± 0.003 µg L and the limit of quantification (LOQ) was 0.303 ± 0.009 µg L. In FAPA-MS, the LOD was 0.050 ± 0.002 µg L and the LOQ was 0.150 ± 0.006 µg L. The content of amygdalin in various matrices was determined.
Topics: Amygdalin; Animals; Antineoplastic Agents; Apoptosis; Atmospheric Pressure; Cell Proliferation; Chromatography, High Pressure Liquid; Humans; Limit of Detection; Neoplasms; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 33086630
DOI: 10.3390/biom10101459 -
Journal of Ethnopharmacology Oct 2021Bitter apricot kernels' extract contains a broad spectrum of biologically active substances with a lot of attention to amygdalin - cyanogenic glycoside. The extract has...
ETHNOPHARMACOLOGICAL RELEVANCE
Bitter apricot kernels' extract contains a broad spectrum of biologically active substances with a lot of attention to amygdalin - cyanogenic glycoside. The extract has been used in the pharmaceutical industry for years as an ingredient of different pharmaceuticals with anti-inflammatory, antimicrobial, or regenerative properties. In traditional medicine, the bitter apricot kernels are known as a remedy for respiratory disorders and skin diseases. The apricot kernels and amygdalin are often prescribed by practitioners for the prevention and treatment of various medical conditions, including colorectal cancer. THE PRESENT STUDY AIMS: to evaluate the phytochemical composition and the potential antimutagenic, antirecombinogenic, and antitumor effect of apricot kernels' extract at very low concentrations in yeast cell-based tests and mammalian hepatocellular and colon carcinoma cell lines.
MATERIALS AND METHODS
Phytochemical analysis was performed by LC-MS profiling. Reverse-phase HPLC and UV detection were applied for the determination of amygdalin quantity in the extract. Biological activity was evaluated by Zimmermann's mutagenicity and Ty1 retrotransposition test. Cytotoxic/antiproliferative activity of apricot kernels' extract was performed on four types of cell lines - HepG2, HT-29, BALB/3T3, clone A31, and BJ using the standard MTT-dye reduction assay.
RESULTS
Data revealed the presence of more than 1000 compounds and 4 cyanogenic glycosides among them - Amygdalin, Deidaclin, Linamarin and Prulaurasin. The Amygdalin concentration was measured to be 57.8 μg/ml. All extract concentrations demonstrated a strong antigenotoxic, antirecombinogenic, antimutagenic, and anticarcinogenic effect in the yeast cell-based tests. High selectivity of the extract action is established among different mammalian cell lines. Normal cell line BJ is found to be resistant to the extract action. HepG2 was found to be the most sensitive to apricot kernels' action.
CONCLUSION
The present study provides the first phytochemical analysis of Bulgarian bitter apricot kernels. Three new cyanogenic glycosides were reported. Evidence is obtained that the apricot kernels' extract at low concentrations is not able to induce some of the events related to the initial steps of tumorigenesis. Additionally, a high selectivity of the extract action is established among different cell lines. The most sensitive cell line was found to be HepG2.
Topics: Amygdalin; Animals; BALB 3T3 Cells; Carcinoma, Hepatocellular; Cell Line; Colorectal Neoplasms; HT29 Cells; Hep G2 Cells; Humans; Liver Neoplasms; Mice; Phytochemicals; Plant Extracts; Prunus armeniaca; Saccharomyces cerevisiae; Seeds
PubMed: 34146630
DOI: 10.1016/j.jep.2021.114333 -
Chemistry & Biodiversity Mar 2023In the processing field, there is a saying that "seed drugs be stir-fried". Bitter almond (BA) is a kind of seed Chinese medicine. BA need be used after being fried. To...
In the processing field, there is a saying that "seed drugs be stir-fried". Bitter almond (BA) is a kind of seed Chinese medicine. BA need be used after being fried. To distinguish raw bitter almonds (RBA) from processed products and prove the rationality of "seed drugs be stir-fried", we analyzed the RBA and five processed products (scalded bitter almonds, fried bitter almonds, honey fried bitter almonds, bran fried bitter almonds, bitter almonds cream) using RP-HPLC fingerprints and chemometric methods. The similarity between RBA and processed products was 0.733∼0.995. Hierarchically clustered heatmap was used to evaluate the changes in components. Principal component analysis (PCA) was used for classification, and all samples are distinguished according to RBA and five processing methods. Six chemical markers were obtained by partial least squares discriminant analysis (PLS-DA). The content and degradation rate of amygdalin and β-glucosidase activity were determined. Compared with RBA, the content and degradation rate of amygdalin, and β-glucosidase activity were increased in bitter almonds cream. The content and degradation rate were decreased, and β-glucosidase was inactivated in other processed products. The above results showed that stir-frying had the best effect. The results showed that processing can ensure the stability of RBA quality, and the saying "seed drugs be stir-fried" is reasonable.
Topics: Amygdalin; Cellulases; Chemometrics; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Prunus dulcis
PubMed: 36747377
DOI: 10.1002/cbdv.202200989 -
Journal of Physiology and Pharmacology... Aug 2019Amygdalin is most commonly occurring cyanogenic glycoside. It is found in seeds of many plant species. Our study was aimed to reveal whether pure intramuscularly...
Amygdalin is most commonly occurring cyanogenic glycoside. It is found in seeds of many plant species. Our study was aimed to reveal whether pure intramuscularly injected amygdalin or apricot seeds peroral exposure cause changes in bone microstructure of rabbits. Twenty clinically healthy 5 months-old male rabbits were segregated into five groups. Animals from groups A1 and A2 were intramuscularly injected with amygdalin at doses of 0.6 and 3 mg/kg b.w. daily for 28 days. The groups S1 and S2 received commercial feed for rabbits mixed with crushed bitter apricot seeds at doses of 60 and 300 mg/kg b.w. during 28 days. The control (C) group did not receive any amygdalin. Intramuscular and peroral amygdalin administration did not affect total body weight, femoral length and femoral weight of rabbits. Similarly, microcomputed tomography (3D analysis) has shown that amygdalin had insignificant effect on relative bone volume, bone mineral density, cortical bone thickness, bone surface, trabecular thickness, trabecular number, trabecular separation. However, histological (2D analysis) revealed evident changes in compact bone microstructure of amygdalin-exposed rabbits consistent with a different vascularization and changed biomechanical properties. We can conclude that subacute exposure to amygdalin (both intramuscular and peroral) at the doses used in our study influenced compact bone remodeling.
Topics: Administration, Oral; Amygdalin; Animals; Antineoplastic Agents, Phytogenic; Bone Remodeling; Femur; Injections, Intramuscular; Male; Rabbits; X-Ray Microtomography
PubMed: 31741461
DOI: 10.26402/jpp.2019.4.15 -
Food & Nutrition Research 2021Coronavirus disease 2019 (COVID-19) outbreak is progressing rapidly, and poses significant threats to public health. A number of clinical practice results showed that...
BACKGROUND
Coronavirus disease 2019 (COVID-19) outbreak is progressing rapidly, and poses significant threats to public health. A number of clinical practice results showed that traditional Chinese medicine (TCM) plays a significant role for COVID-19 treatment.
OBJECTIVE
To explore the active components and molecular mechanism of semen treating COVID-19 by network pharmacology and molecular docking technology.
METHODS
The active components and potential targets of semen were retrieved from traditional Chinese medicine systems pharmacology (TCMSP) database. Coronavirus disease 2019-associated targets were collected in the GeneCards, TTD, OMIM and PubChem database. Compound target, compound-target pathway and medicine-ingredient-target disease networks were constructed by Cytoscape 3.8.0. Protein-protein interaction (PPI) networks were drawn using the STRING database and Cytoscape 3.8.0 software. David database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The main active components were verified by AutoDock Vina 1.1.2 software. A lipopolysaccharide (LPS)-induced lung inflammation model in Institute of Cancer Research (ICR) mice was constructed and treated with amygdalin to confirm effects of amygdalin on lung inflammation and its underlying mechanisms by western blot analyses and immunofluorescence.
RESULTS
The network analysis revealed that nine key, active components regulated eight targets (Proto-oncogene tyrosine-protein kinase SRC (SRC), interleukin 6 (IL6), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 3 (MAPK3), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), HRAS proto-oncogene (HRAS), caspase-3 (CASP3)). Gene ontology and KEGG enrichment analysis suggested that semen plays a role in COVID-19 by modulating 94 biological processes, 13 molecular functions, 15 cellular components and 80 potential pathways. Molecular docking indicated that amygdalin had better binding activity to key targets such as IL6, SRC, MAPK3, SARS coronavirus-2 3C-like protease (SARS-CoV-2 3CLpro) and SARS-CoV-2 angiotensin converting enzyme II (ACE2). Experimental validation revealed that the lung pathological injury and inflammatory injury were significantly increased in the model group and were improved in the amygdalin group.
CONCLUSION
Amygdalin is a candidate compound for COVID-19 treatment by regulating IL6, SRC, MAPK1 EGFR and VEGFA to involve in PI3K-Akt signalling pathway, VEGF signalling pathway and MAPK signalling pathway. Meanwhile, amygdalin has a strong affinity for SARS-CoV-2 3CLpro and SARS-CoV-2 ACE2 and therefore prevents the virus transcription and dissemination.
PubMed: 34908920
DOI: 10.29219/fnr.v65.5623