12-O-Tetradecanoylphorbol-13-acetate


12-O-Tetradecanoylphorbol-13-acetate, also commonly known as tetradecanoylphorbol acetate, tetradecanoyl phorbol acetate, and phorbol 12-myristate 13-acetate, is a diester of phorbol and a potent tumor promoter often employed in biomedical research to activate the signal transduction enzyme protein kinase C. 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. Thus, TPA/PMA has been routinely used as an inducer for endogenous superoxide production.
TPA is also being studied as a drug in the treatment of hematologic cancer
TPA has a specific use in cancer diagnostics as a B-cell specific mitogen in cytogenetic testing. To view the chromosomes, a cytogenetic test requires dividing cells. TPA is used to stimulate division of B-cells during cytogenetic diagnosis of B-cell cancers such as chronic lymphocytic leukemia.
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.
TPA induces KSHV reactivation in PEL cell cultures via stimulation of the mitogen-activated protein kinase /extracellular signal-regulated kinase pathway. The pathway involves the activation of the early-immediate viral protein RTA that contributes to the activation of the lytic cycle.
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.