Chemistry:12-O-Tetradecanoylphorbol-13-acetate
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| 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. | |
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3D model (JSmol)
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| Properties | |
| C36H56O8 | |
| 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). | |
 verify (what is   ?)
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| Infobox references | |
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.
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
- ↑ Castagna (1982). "Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters". Journal of Biological Chemistry 257 (13): 7847–7851. doi:10.1016/S0021-9258(18)34459-4. PMID 7085651. http://www.jbc.org/content/257/13/7847.full.pdf.
- ↑ 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. doi:10.1073/pnas.80.1.36. PMID 6296873. Bibcode: 1983PNAS...80...36N.
- ↑ 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". The Journal of Immunology 169 (10): 5866–5873. doi:10.4049/jimmunol.169.10.5866. PMID 12421969. http://www.jimmunol.org/content/169/10/5866.full.pdf.
- ↑ Huang (2014). "Megakaryocytic Differentiation of K562 Cells Induced by PMA Reduced the Activity of Respiratory Chain Complex IV". PLoS ONE 9 (5): e96246. doi:10.1371/journal.pone.0096246. PMID 24817082. Bibcode: 2014PLoSO...996246H.
- ↑ 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. http://www.ebioscience.com/resources/best-protocols/flow-cytometry/flow-cytometry-intracellular-staining-quick-guide.htm.
- ↑ 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. 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 et al. (June 2006). "A phase I clinical trial of 12- O-tetradecanoylphorbol-13-acetate for patients with relapsed/refractory malignancies" (in en). Cancer Chemotherapy and Pharmacology 57 (6): 789–795. doi:10.1007/s00280-005-0125-1. ISSN 1432-0843. PMID 16231182. https://link.springer.com/article/10.1007/s00280-005-0125-1.
External links
- Tetradecanoylphorbol+Acetate at the US National Library of Medicine Medical Subject Headings (MeSH)
- "NCI Dictionary Entry". http://www.cancer.gov/dictionary?CdrID=46763.
- "Phase 1 Clinical Trials". http://www.clinicaltrials.gov/ct/show/NCT00004058.
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