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 terpene, diterpenes. Phorbol was first isolated in 1934 via the hydrolysis of croton oil, which is derived from the seeds of the purging croton, ''Crot ...

. It is a potent

tumor promoter Tumor promotion is a process in carcinogenesis by which various factors permit the descendants of a single initiated cell to survive and expand in number, i.e. to resist apoptosis and to undergo clonal growth. This is a step toward tumor progressi ...

often employed in biomedical research to activate the

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

protein kinase C In cell biology, protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...

(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. Diglycerides are n ...

. TPA is a

small molecule In 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 are small molecules; ...

drug. In

ROS Ros or ROS or RoS may refer to: Organizations * Raggruppamento Operativo Speciale, the Anti-organized Crime Branch of the Italian Carabinieri * Registers of Scotland, a Scottish authority responsible for compiling and maintaining records * Repart ...

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 A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

in the treatment of hematologic

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

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 cell cycle Mitogens 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. 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 Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow. In CLL, the bone marrow makes too many lymphocytes, which are a type of white blood cell. In patients with CLL, B cell lymphocytes can begin to colle ...

. 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 Poison ivy is a type of allergenic plant in the genus '' Toxicodendron'' native to Asia and North America. Formerly considered a single species, '' Toxicodendron radicans'', poison ivies are now generally treated as a complex of three separate s ...

-like rash. It underwent a phase 1

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

References

External links

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