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Annals of the New York Academy of... 1983The evidence for the multistage nature of tumor promotion in vivo and for multiple subclasses of phorbol ester receptors in vitro argues that multiple mechanisms of... (Review)
Review
The evidence for the multistage nature of tumor promotion in vivo and for multiple subclasses of phorbol ester receptors in vitro argues that multiple mechanisms of tumor promotion exist. The existence of multiple mechanisms suggests that brute force assay for tumor promoters in vivo may be inadequate and that understanding of mechanisms may be essential. The interest in the phorbol esters is not primarily that they are environmental hazards for man, but rather that they provide a probe for phorbol ester receptors. These receptors are found in people, and modulation of their activity may play a role in tumor promotion in man.
Topics: Animals; Caenorhabditis elegans Proteins; Carrier Proteins; Mice; Neoplasms, Experimental; Phorbol 12,13-Dibutyrate; Phorbol Esters; Phorbols; Protein Kinase C; Receptors, Cell Surface; Receptors, Drug; Skin Neoplasms; Structure-Activity Relationship
PubMed: 6309054
DOI: 10.1111/j.1749-6632.1983.tb47836.x -
Carcinogenesis; a Comprehensive Survey 1982
Review
Topics: Animals; Binding Sites; Biological Transport; Blood Physiological Phenomena; Caenorhabditis elegans Proteins; Calcium; Carcinogens; Carrier Proteins; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Cells, Cultured; Cocarcinogenesis; Cytosol; Mutation; Phorbol Esters; Phorbols; Phospholipids; Polycyclic Compounds; Protein Kinase C; Receptors, Drug; Structure-Activity Relationship
PubMed: 7039835
DOI: No ID Found -
Critical Reviews in Toxicology Jun 1981
Review
Topics: Animals; Cell Differentiation; Cell Line; Cell Transformation, Neoplastic; Clone Cells; DNA Repair; Models, Biological; Mutagens; Mutation; Neoplasms, Experimental; Phorbol Esters; Phorbols; Structure-Activity Relationship; Tetradecanoylphorbol Acetate
PubMed: 7018838
DOI: 10.3109/10408448109109658 -
Chemical & Pharmaceutical Bulletin Feb 2002Anaerobic incubation of phorbol (1) from Croton tiglium with human intestinal bacteria afforded five metabolites: isophorbol (2), deoxyphorbol (3),...
Anaerobic incubation of phorbol (1) from Croton tiglium with human intestinal bacteria afforded five metabolites: isophorbol (2), deoxyphorbol (3), 4beta,9alpha,20-trihydroxy-13,15-seco-1,6,15-tigliatriene-3,13-dione (4), 4beta,9alpha,20-trihydroxy-15,16,17-trinor-1,6-tigliadiene-3,13-dione (5) and 4beta,9a,20-trihydroxy-14(13-->12)-abeo-12alphaH-1,6-tigliadiene-3,13-dione (6). All these metabolites (2-6) were identified and characterized by spectroscopic means, including two-dimensional (2D)-NMR. Nine defined strains from the human intestine showed an ability to transform 1 to these metabolites.
Topics: Bacteria; Biotransformation; Humans; Intestines; Magnetic Resonance Spectroscopy; Phorbols
PubMed: 11848202
DOI: 10.1248/cpb.50.160 -
Critical Reviews in Toxicology Dec 1980
Comparative Study Review
Topics: Animals; Blood Cells; Cell Membrane; Cell Transformation, Neoplastic; Cells, Cultured; Chick Embryo; Hormones; Humans; Mice; Microtubules; Mitosis; Nucleotides, Cyclic; Phorbol Esters; Phorbols; Phospholipids; Polyamines; Tetradecanoylphorbol Acetate
PubMed: 7002476
DOI: 10.3109/10408448009037493 -
International Journal of Molecular... Apr 2022Megakaryocytes are large hematopoietic cells present in the bone marrow cavity, comprising less than 0.1% of all bone marrow cells. Despite their small number,...
Megakaryocytes are large hematopoietic cells present in the bone marrow cavity, comprising less than 0.1% of all bone marrow cells. Despite their small number, megakaryocytes play important roles in blood coagulation, inflammatory responses, and platelet production. However, little is known about changes in gene expression during megakaryocyte maturation. Here we identified the genes whose expression was changed during K562 leukemia cell differentiation into megakaryocytes using an Affymetrix GeneChip microarray to determine the multifunctionality of megakaryocytes. K562 cells were differentiated into mature megakaryocytes by treatment for 7 days with phorbol 12-myristate 13-acetate, and a microarray was performed using RNA obtained from both types of cells. The expression of 44,629 genes was compared between K562 cells and mature megakaryocytes, and 954 differentially expressed genes (DEGs) were selected based on a p-value < 0.05 and a fold change >2. The DEGs was further functionally classified using five major megakaryocyte function-associated clusters—inflammatory response, angiogenesis, cell migration, extracellular matrix, and secretion. Furthermore, interaction analysis based on the STRING database was used to generate interactions between the proteins translated from the DEGs. This study provides information on the bioinformatics of the DEGs in mature megakaryocytes after K562 cell differentiation.
Topics: Acetates; Cell Differentiation; Computational Biology; Humans; K562 Cells; Megakaryocytes; Microarray Analysis; Myristic Acid; Phorbols; Tetradecanoylphorbol Acetate; Thrombopoiesis
PubMed: 35457039
DOI: 10.3390/ijms23084221 -
International Journal of Molecular... Feb 2023Protein kinase C delta (PKC-δ) is an important signaling molecule in human cells that has both proapoptotic as well as antiapoptotic functions. These conflicting...
Protein kinase C delta (PKC-δ) is an important signaling molecule in human cells that has both proapoptotic as well as antiapoptotic functions. These conflicting activities can be modulated by two classes of ligands, phorbol esters and bryostatins. Phorbol esters are known tumor promoters, while bryostatins have anti-cancer properties. This is despite both ligands binding to the C1b domain of PKC-δ (δC1b) with a similar affinity. The molecular mechanism behind this discrepancy in cellular effects remains unknown. Here, we have used molecular dynamics simulations to investigate the structure and intermolecular interactions of these ligands bound to δC1b with heterogeneous membranes. We observed clear interactions between the δC1b-phorbol complex and membrane cholesterol, primarily through the backbone amide of L250 and through the K256 side-chain amine. In contrast, the δC1b-bryostatin complex did not exhibit interactions with cholesterol. Topological maps of the membrane insertion depth of the δC1b-ligand complexes suggest that insertion depth can modulate δC1b interactions with cholesterol. The lack of cholesterol interactions suggests that bryostatin-bound δC1b may not readily translocate to cholesterol-rich domains within the plasma membrane, which could significantly alter the substrate specificity of PKC-δ compared to δC1b-phorbol complexes.
Topics: Humans; Protein Kinase C-delta; Bryostatins; Isoenzymes; Phorbol Esters; Phorbols; Lactones
PubMed: 36902029
DOI: 10.3390/ijms24054598 -
Journal of the American Chemical Society Jun 2001
Topics: Carcinogens; Phorbols; Stereoisomerism
PubMed: 11389648
DOI: 10.1021/ja010643u -
Journal of Separation Science Apr 2023Phorbol is a tetracyclic diterpenoid found in Euphorbia tirucalli, Croton tiglium, and Rehmannia glutinosa, and is nuclear of various phorbol esters. The rapid...
Phorbol is a tetracyclic diterpenoid found in Euphorbia tirucalli, Croton tiglium, and Rehmannia glutinosa, and is nuclear of various phorbol esters. The rapid obtaining of phorbol with high purity highly contributes to its application, such as synthesizing phorbol esters with designable side chains and particular therapeutic efficacy. This study introduced a biphasic alcoholysis method for obtaining phorbol from croton oil by using polarity imparity organic solvents in both phases and established a high-speed countercurrent chromatography method for simultaneous separation and purification of phorbol. The optimized operation conditions of biphasic alcoholysis were a reaction time of 91 min, a temperature of 14°C, and a croton oil-methanol ratio of 1:30 (g:ml). The phorbol during the biphasic alcoholysis was 3.2-fold higher in content than that obtained in conventional monophasic alcoholysis. The optimized high-speed countercurrent chromatography method was using the ethyl acetate/n-butyl alcohol/water at 4.7:0.3:5 (v:v:v) with Na SO at 0.36 g/10 ml as the solvent system, using the mobile phase flow rate of 2 ml/min, the revolution of 800 r/min, under which the retention of the stationary phase was achieved at 72.83%. The crystallized phorbol following high-speed countercurrent chromatography was obtained as high purity of 94%.
Topics: Countercurrent Distribution; Croton Oil; Solvents; Plant Extracts; Phorbols; Phorbol Esters; Chromatography, High Pressure Liquid
PubMed: 36795010
DOI: 10.1002/jssc.202200984 -
Journal of Asian Natural Products... 2013The phytochemical investigation of the flower buds of Daphne genkwa yielded four highly oxygenated tigliane diterpene esters (1-4), including two new phorbol...
The phytochemical investigation of the flower buds of Daphne genkwa yielded four highly oxygenated tigliane diterpene esters (1-4), including two new phorbol derivatives, 12-O-(2'E,4'E-decadienoyl)-7-oxo-5-ene-phorbol-13-acetate (1) and 12-O-neodecanoyl-7-oxo-5-ene-phorbol-13-acetate (2). The molecular structures of the isolated compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR.
Topics: Daphne; Diterpenes; Drugs, Chinese Herbal; Esters; Flowers; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Phorbols
PubMed: 23600859
DOI: 10.1080/10286020.2013.786703