12-O-Tetradecanoylphorbol-13-acetate explained
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 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. It underwent a phase 1 clinical trial.[9]
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Notes and References
- Castagna . 1982 . Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters . . 257 . 13 . 7847–7851 . 10.1016/S0021-9258(18)34459-4 . 7085651. free .
- Blumberg . 1988 . Protein kinase C as the receptor for the phorbol ester tumor promoters: sixth Rhoads memorial award lecture. . 48 . 1. 1–8. 3275491.
- Niedel . 1983 . . 80 . 36–40 . 10.1073/pnas.80.1.36 . Phorbol Diester Receptor Copurifies with Protein Kinase C . 1 . 1983PNAS...80...36N . 393304 . 6296873. free .
- 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. . 169 . 10 . 5866–5873 . 10.4049/jimmunol.169.10.5866. 12421969 . 21433304 . free .
- Huang . 2014 . Megakaryocytic Differentiation of K562 Cells Induced by PMA Reduced the Activity of Respiratory Chain Complex IV . . 9 . 5 . e96246 . 10.1371/journal.pone.0096246. 2014PLoSO...996246H . 4015910 . 24817082. free .
- The AGT cytogenetics laboratory manual. 3rd ed. Barch, Margaret J., Knutsen, Turid., Spurbeck, Jack L., eds. 1997. Lippincott-Raven.
- Web site: Flow Cytometry Intracellular Staining Guide . eBioscience, Inc . 2011-09-25 .
- Cohen. Adina. Brodie. Chaya. Sarid. Ronit. An essential role of ERK signalling in TPA-induced reactivation of Kaposi's sarcoma-associated herpesvirus.. The Journal of General Virology. April 2006. 87. Pt 4. 795–802. 16528027. 10.1099/vir.0.81619-0. 10.1.1.321.5484.
- 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. . A phase I clinical trial of 12- O-tetradecanoylphorbol-13-acetate for patients with relapsed/refractory malignancies . Cancer Chemotherapy and Pharmacology . June 2006 . 57 . 6 . 789–795 . 10.1007/s00280-005-0125-1 . 16231182 . 33377618 . en . 1432-0843.
