The term 'phorbol' is used to describe the family of naturally occurring compounds that can be referred to as tigliane diterpenes. Phorbol esters are the tetracyclic diterpenoids generally known for their tumor promoting activity. The phorbol esters mimic the action of diacyl glycerol (DAG), activator of protein kinase C, which regulates different signal transduction pathways and other cellular metabolic activities. The biological activities of the phorbol esters are highly structure specific. The phorbol esters, even at very low concentrations, show toxicological manifestations in animals fed diets containing them. This toxicity limits the use of many nutritive plants and agricultural by-products containing phorbol esters to be used as animal feed. Besides, possessing antinutritional and toxic effects, few derivatives of the phorbol esters are also known for their antimicrobial and antitumor activities. The molluscicidal and insecticidal properties of phorbol esters indicate its potential to be used as an effective biopesticide and insecticide. The phorbols themselves do not induce tumors but promote tumor growth following exposure to a subcarcinogenic dose of a carcinogen. TPA and related phorbols were reported to be a potent stimulator for plasminogen activator synthesis. A good correlation was observed between plasminogen activator induction and tumor promotion with TPA, phorbol 12,13-didecanoate (PDD), and TPA beta-oxide (a derivative of TPA) in bioassays. The phorbol does not involve covalent binding to the cellular DNA, in fact it mimics the effects of transformation such as alteration in membrane morphology, increased saturation density, altered cell surface fucose glycopeptides, and increased the level of plasminogen activator and ornithine decarboxylase. (A15429) Various esters of phorbol have important biological properties, the most notable of which is the capacity to act as tumor promoters through activation of protein kinase C. They mimic diacylglycerols, glycerol derivatives in which two hydroxyl groups have reacted with fatty acids to form esters. The most common phorbol ester is 12-O-tetradecanoylphorbol-13-acetate (TPA), also called phorbol-12-myristate-13-acetate (PMA), which is used as a biomedical research tool in models of carcinogenesis. TPA, together with ionomycin, can also be used to stimulate T-cell activation, proliferation, and cytokine production, and is used in protocols for intracellular staining of these cytokines. (Wikipedia)