12-O-Tetradecanoylphorbol-13-acetate
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).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> Thus, TPA/PMA has been routinely used as an inducer for endogenous superoxide production.<ref>Template:Cite journal</ref>
TPA is also being studied as a drug in the treatment of hematologic cancer Template: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.<ref>The AGT cytogenetics laboratory manual. 3rd ed. Barch, Margaret J., Knutsen, Turid., Spurbeck, Jack L., eds. 1997. Lippincott-Raven.</ref>
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.<ref name="urlFlow Cytometry Intracellular Staining Guide">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
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.<ref>Template:Cite journal</ref>
TPA was first found in the Croton plant, a shrub found in Southeast Asia, exposure to which provokes a poison ivy-like rash.Template:Citation needed It underwent a phase 1 clinical trial.<ref>Template:Cite journal</ref>
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