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 Phorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. Phorbol was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of the purging croton, ''Croton ...

. It is a potent tumor promoter often employed in biomedical research to activate the signal transduction

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

protein kinase C (PKC). The effects of TPA on PKC result from its similarity to one of the natural activators of classic PKC isoforms,

diacylglycerol A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as s ...

. TPA is a

small molecule Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ...

drug. In ROS biology,

superoxide In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...

was identified as the major reactive oxygen species induced by TPA/PMA but not by

ionomycin Ionomycin is an ionophore and an antibiotic that binds calcium ions (Ca2+) in a ratio 1:1. It is produced by the bacterium '' Streptomyces conglobatus''. It binds also other divalent cations like magnesium and cadmium, but binds Ca2+ preferably. I ...

in mouse macrophages. Thus, TPA/PMA has been routinely used as an inducer for endogenous

production. TPA is also being studied as a drug in the treatment of

hematologic Hematology ( always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the produc ...

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

TPA has a specific use in cancer diagnostics as a B-cell specific

mitogen A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The mechanism of action of a ...

cytogenetic Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...

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

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 (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. 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 Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

References

External links

* * * {{DEFAULTSORT:Tetradecanoylphorbol-13-acetate, 12-O- Diterpenes Carcinogens Acetate esters Cyclopropanes Cyclopentenes Phorbol esters