12-O-Tetradecanoylphorbol-13-acetate (TPA), also commonly known as tetradecanoylphorbol acetate, tetradecanoyl phorbol acetate, and phorbol 12-myristate 13-acetate (PMA) is a diester of phorbol. It is a potent tumor promoter often employed in biomedical research to activate the signal transductionenzymeprotein kinase C (PKC).[1][2][3] The effects of TPA on PKC result from its similarity to one of the natural activators of classic PKC isoforms, diacylglycerol. TPA is a small molecule drug.
In ROS biology, superoxide was identified as the major reactive oxygen species induced by TPA/PMA but not by ionomycin in mouse macrophages.[4] Thus, TPA/PMA has been routinely used as an inducer for endogenous superoxide production.[5]
TPA has a specific use in cancer diagnostics as a B-cell specific mitogen in cytogenetic testing. Cells must be divided in a cytogenic test to view the chromosomes. TPA is used to stimulate division of B-cells during cytogenetic diagnosis of B-cell cancers such as chronic lymphocytic leukemia.[6]
TPA is also commonly used together with ionomycin to stimulate T-cell activation, proliferation, and cytokine production, and is used in protocols for intracellular staining of these cytokines.[7]
TPA induces KSHV reactivation in PEL cell cultures via stimulation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. The pathway involves the activation of the early-immediate viral protein RTA that contributes to the activation of the lytic cycle.[8]
^Castagna (1982). "Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters" (PDF). Journal of Biological Chemistry. 257 (13): 7847–7851. doi:10.1016/S0021-9258(18)34459-4. PMID 7085651.
^Blumberg (1988). "Protein kinase C as the receptor for the phorbol ester tumor promoters: sixth Rhoads memorial award lecture". Cancer Research. 48 (1): 1–8. PMID 3275491.
^Swindle (2002). "A Comparison of Reactive Oxygen Species Generation by Rat Peritoneal Macrophages and Mast Cells Using the Highly Sensitive Real-Time Chemiluminescent Probe Pholasin: Inhibition of Antigen-Induced Mast Cell Degranulation by Macrophage-Derived Hydrogen Peroxide" (PDF). The Journal of Immunology. 169 (10): 5866–5873. doi:10.4049/jimmunol.169.10.5866. PMID 12421969. S2CID 21433304.
^Huang (2014). "Megakaryocytic Differentiation of K562 Cells Induced by PMA Reduced the Activity of Respiratory Chain Complex IV". PLoS ONE. 9 (5): e96246. Bibcode:2014PLoSO...996246H. doi:10.1371/journal.pone.0096246. PMC4015910. PMID 24817082.
^The AGT cytogenetics laboratory manual. 3rd ed. Barch, Margaret J., Knutsen, Turid., Spurbeck, Jack L., eds. 1997. Lippincott-Raven.
^"Flow Cytometry Intracellular Staining Guide". eBioscience, Inc. Retrieved 2011-09-25.
^Cohen, Adina; Brodie, Chaya; Sarid, Ronit (April 2006). "An essential role of ERK signalling in TPA-induced reactivation of Kaposi's sarcoma-associated herpesvirus". The Journal of General Virology. 87 (Pt 4): 795–802. CiteSeerX10.1.1.321.5484. doi:10.1099/vir.0.81619-0. PMID 16528027.
^Schaar, Dale; Goodell, Lauri; Aisner, Joseph; Cui, Xiao Xing; Han, Zheng Tao; Chang, Richard; Martin, John; Grospe, Stephanie; Dudek, Liesel; Riley, Joan; Manago, Jacqueline; Lin, Yong; Rubin, Eric H.; Conney, Allan; Strair, Roger K. (June 2006). "A phase I clinical trial of 12- O-tetradecanoylphorbol-13-acetate for patients with relapsed/refractory malignancies". Cancer Chemotherapy and Pharmacology. 57 (6): 789–795. doi:10.1007/s00280-005-0125-1. ISSN 1432-0843. PMID 16231182. S2CID 33377618.
External linksedit
Tetradecanoylphorbol+Acetate at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
"NCI Dictionary Entry". Retrieved 2005-07-02.
"Phase 1 Clinical Trials". Retrieved 2005-07-02.
May 07, 2024
tetradecanoylphorbol, acetate, also, commonly, known, tetradecanoylphorbol, acetate, tetradecanoyl, phorbol, acetate, phorbol, myristate, acetate, diester, phorbol, potent, tumor, promoter, often, employed, biomedical, research, activate, signal, transduction,. 12 O Tetradecanoylphorbol 13 acetate TPA also commonly known as tetradecanoylphorbol acetate tetradecanoyl phorbol acetate and phorbol 12 myristate 13 acetate PMA is a diester of phorbol It is a potent tumor promoter often employed in biomedical research to activate the signal transduction enzyme protein kinase C PKC 1 2 3 The effects of TPA on PKC result from its similarity to one of the natural activators of classic PKC isoforms diacylglycerol TPA is a small molecule drug 12 O Tetradecanoylphorbol 13 acetate Names Preferred IUPAC name 1aR 1bS 4aR 7aS 7bS 8R 9R 9aS 4a 7b Dihydroxy 3 hydroxymethyl 1 1 6 8 tetramethyl 5 oxo 1 1a 1b 4 4a 5 7a 7b 8 9 decahydro 9aH cyclopropa 3 4 benzo 1 2 e azulene 9 9a diyl 9a acetate 9 tetradecanoate Other names TPA PMA Phorbol myristate acetate Tetradecanoylphorbol acetate Identifiers CAS Number 16561 29 8 Y 3D model JSmol Interactive imageInteractive image ChEBI CHEBI 37537 N ChEMBL ChEMBL279115 N ChemSpider 25977 N ECHA InfoCard 100 109 485 IUPHAR BPS 2341 KEGG C05151 N PubChem CID 27924 UNII NI40JAQ945 Y CompTox Dashboard EPA DTXSID5023798 InChI InChI 1S C36H56O8 c1 7 8 9 10 11 12 13 14 15 16 17 18 29 39 43 32 24 3 35 42 27 30 33 5 6 36 30 32 44 25 4 38 20 26 22 37 21 34 41 28 35 19 23 2 31 34 40 h19 20 24 27 28 30 32 37 41 42H 7 18 21 22H2 1 6H3 t24 27 28 30 32 34 35 36 m1 s1 NKey PHEDXBVPIONUQT RGYGYFBISA N NInChI 1 C36H56O8 c1 7 8 9 10 11 12 13 14 15 16 17 18 29 39 43 32 24 3 35 42 27 30 33 5 6 36 30 32 44 25 4 38 20 26 22 37 21 34 41 28 35 19 23 2 31 34 40 h19 20 24 27 28 30 32 37 41 42H 7 18 21 22H2 1 6H3 t24 27 28 30 32 34 35 36 m1 s1Key PHEDXBVPIONUQT RGYGYFBIBK SMILES CCCCCCCCCCCCCC O O C H 1 C H C 2 C H C C C C 3 C H 2C C C3 O C O CO C H 4 C 1 C4 C C OC O C O CCCCCCCCCCCCCCC O O C H 2C C C 1 O C4 C C C C O C 4 O CC CO C C H 1 C H 3 C 2 OC C O C3 C C Properties Chemical formula C 36H 56O 8 Molar mass 616 83 g mol Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references In ROS biology superoxide was identified as the major reactive oxygen species induced by TPA PMA but not by ionomycin in mouse macrophages 4 Thus TPA PMA has been routinely used as an inducer for endogenous superoxide production 5 TPA is also being studied as a drug in the treatment of hematologic cancer citation needed TPA has a specific use in cancer diagnostics as a B cell specific mitogen in cytogenetic testing Cells must be divided in a cytogenic test to view the chromosomes TPA is used to stimulate division of B cells during cytogenetic diagnosis of B cell cancers such as chronic lymphocytic leukemia 6 TPA is also commonly used together with ionomycin to stimulate T cell activation proliferation and cytokine production and is used in protocols for intracellular staining of these cytokines 7 TPA induces KSHV reactivation in PEL cell cultures via stimulation of the mitogen activated protein kinase MAPK extracellular signal regulated kinase ERK pathway The pathway involves the activation of the early immediate viral protein RTA that contributes to the activation of the lytic cycle 8 TPA was first found in the Croton plant a shrub found in Southeast Asia exposure to which provokes a poison ivy like rash citation needed It underwent a phase 1 clinical trial 9 References edit Castagna 1982 Direct activation of calcium activated phospholipid dependent protein kinase by tumor promoting phorbol esters PDF Journal of Biological Chemistry 257 13 7847 7851 doi 10 1016 S0021 9258 18 34459 4 PMID 7085651 Blumberg 1988 Protein kinase C as the receptor for the phorbol ester tumor promoters sixth Rhoads memorial award lecture Cancer Research 48 1 1 8 PMID 3275491 Niedel 1983 Phorbol Diester Receptor Copurifies with Protein Kinase C Proceedings of the National Academy of Sciences 80 1 36 40 Bibcode 1983PNAS 80 36N doi 10 1073 pnas 80 1 36 PMC 393304 PMID 6296873 Swindle 2002 A Comparison of Reactive Oxygen Species Generation by Rat Peritoneal Macrophages and Mast Cells Using the Highly Sensitive Real Time Chemiluminescent Probe Pholasin Inhibition of Antigen Induced Mast Cell Degranulation by Macrophage Derived Hydrogen Peroxide PDF The Journal of Immunology 169 10 5866 5873 doi 10 4049 jimmunol 169 10 5866 PMID 12421969 S2CID 21433304 Huang 2014 Megakaryocytic Differentiation of K562 Cells Induced by PMA Reduced the Activity of Respiratory Chain Complex IV PLoS ONE 9 5 e96246 Bibcode 2014PLoSO 996246H doi 10 1371 journal pone 0096246 PMC 4015910 PMID 24817082 The AGT cytogenetics laboratory manual 3rd ed Barch Margaret J Knutsen Turid Spurbeck Jack L eds 1997 Lippincott Raven Flow Cytometry Intracellular Staining Guide eBioscience Inc Retrieved 2011 09 25 Cohen Adina Brodie Chaya Sarid Ronit April 2006 An essential role of ERK signalling in TPA induced reactivation of Kaposi s sarcoma associated herpesvirus The Journal of General Virology 87 Pt 4 795 802 CiteSeerX 10 1 1 321 5484 doi 10 1099 vir 0 81619 0 PMID 16528027 Schaar Dale Goodell Lauri Aisner Joseph Cui Xiao Xing Han Zheng Tao Chang Richard Martin John Grospe Stephanie Dudek Liesel Riley Joan Manago Jacqueline Lin Yong Rubin Eric H Conney Allan Strair Roger K June 2006 A phase I clinical trial of 12 O tetradecanoylphorbol 13 acetate for patients with relapsed refractory malignancies Cancer Chemotherapy and Pharmacology 57 6 789 795 doi 10 1007 s00280 005 0125 1 ISSN 1432 0843 PMID 16231182 S2CID 33377618 External links editTetradecanoylphorbol Acetate at the U S National Library of Medicine Medical Subject Headings MeSH NCI Dictionary Entry Retrieved 2005 07 02 Phase 1 Clinical Trials Retrieved 2005 07 02 Retrieved from https en wikipedia org w index php title 12 O Tetradecanoylphorbol 13 acetate amp oldid 1169930089, wikipedia, wiki, book, books, library,
