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Phorbol Esters
Phorbol esters are a class of chemical compounds found in a variety of plants, particularly in the families Euphorbiaceae and Thymelaeaceae. Chemically, they are ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ... derivative (chemistry), derivatives of the tetracyclic diterpenoid phorbol. Biological activity Protein kinase C (PKC) is a phorbol ester receptor. Phorbol esters can stimulate PKC in a similar way to Diglyceride, diglycerides. Phorbol esters are known for their ability to Tumor promotion, promote tumors. In particular, 12-O-tetradecanoylphorbol-13-acetate (TPA) is used as a biomedical research tool in models of carcinogenesis. Plants that contain phorbol esters are often Poison, poisonous. References

{{Chem-stub Phorbol esters, Diterpenes Carboxylate esters ...
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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). 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 di ...
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Tumor Promotion
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 progression. In order for a tumor cell to survive, it must decrease its expression of tumor suppressor genes such as p53, BRCA1, BRCA2, RB1, or the fas receptor. A tumor suppressor would trigger an apoptotic pathway in a cancer cell if there were DNA damage, polyploidy, or uncontrolled cell growth. Simultaneously, tumor cells need to upregulate oncogenes, which promote or cause downstream activation of growth factors and cell survival signals such as RAS, Mitogen-activated protein kinase kinase, VEGF, or Akt. See also * Phorbol myristate acetate * Tumor initiation * Tumor progression Tumor progression is the third and last phase in tumor development. This phase is characterised by increased growth speed and invasiveness of the tumor cells. ...
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Carboxylate Esters
In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylate esters'' have the general formula (or ). R and R′ are organic groups; R′ ≠ H. Synthesis Carboxylate ions can be formed by deprotonation of carboxylic acids. Such acids typically have p''K''a of less than 5, meaning that they can be deprotonated by many bases, such as sodium hydroxide or sodium bicarbonate. :RCOOH + NaOH -> RCOONa + H2O Resonance stabilization of the carboxylate ion Carboxylic acids easily dissociate into a carboxylate anion and a positively charged hydrogen ion (proton), much more readily than alcohols do (into an alkoxide ion and a proton), because the carboxylate ion is stabilized by resonance. The negative charge that is left after deprotonation of the carboxyl group is delocalized between the ...
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Diterpenes
Diterpenes are a class of chemical compounds composed of four isoprene units, often with the molecular formula C20H32. They are biosynthesized by plants, animals and fungi via the HMG-CoA reductase pathway, with geranylgeranyl pyrophosphate being a primary intermediate. Diterpenes form the basis for biologically important compounds such as retinol, retinal, and phytol. They are known to be antimicrobial and antiinflammatory. Structures As with most terpenes a huge number of potential structures exists, which may be broadly divided according to the number of rings present. Biosynthesis Diterpenes are derived from the addition of one IPP unit to FPP to form geranylgeranyl-pyrophosphate (GGPP). From GGPP, structural diversity is achieved mainly by two classes of enzymes; the diterpene synthases and cytochromes P450. Several diterpenes are produced by plants and cyanobacteria. GGPP is also the precursor for the synthesis of the phytane by the action of the enzyme geranylger ...
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Phorbol Esters
Phorbol esters are a class of chemical compounds found in a variety of plants, particularly in the families Euphorbiaceae and Thymelaeaceae. Chemically, they are ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ... derivative (chemistry), derivatives of the tetracyclic diterpenoid phorbol. Biological activity Protein kinase C (PKC) is a phorbol ester receptor. Phorbol esters can stimulate PKC in a similar way to Diglyceride, diglycerides. Phorbol esters are known for their ability to Tumor promotion, promote tumors. In particular, 12-O-tetradecanoylphorbol-13-acetate (TPA) is used as a biomedical research tool in models of carcinogenesis. Plants that contain phorbol esters are often Poison, poisonous. References

{{Chem-stub Phorbol esters, Diterpenes Carboxylate esters ...
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Poison
Poison is a chemical substance that has a detrimental effect to life. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figuratively, with a broad sense. Whether something is considered a poison may change depending on the amount, the circumstances, and what living things are present. Poisoning could be accidental or deliberate, and if the cause can be identified there may be ways to neutralise the effects or minimise the symptoms. In biology, a poison is a chemical substance causing death, injury or harm to organisms or their parts. In medicine, poisons are a kind of toxin that are delivered passively, not actively. In industry the term may be negative, something to be removed to make a thing safe, or positive, an agent to limit unwanted pests. In ecological terms, poisons introduced into the environment can later cause unwanted effects elsewhere, or in other parts of the food ...
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Carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Normally, the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by interfering with the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. Only certain mutations lead to cancer w ...
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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). 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 di ...
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Diglyceride
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 surfactants and are commonly used as emulsifiers in processed foods. DAG-enriched oil (particularly 1,3-DAG) has been investigated extensively as a fat substitute due to its ability to suppress the accumulation of body fat; with total annual sales of approximately USD 200 million in Japan since its introduction in the late 1990s till 2009. Production Diglycerides are a minor component of many seed oils and are normally present at ~1–6%; or in the case of cottonseed oil as much as 10%. Industrial production is primarily achieved by a glycerolysis reaction between triglycerides and glycerol. The raw materials for this may be either vegetable oils or animal fats. Food additive Diglycerides, generally in a mix with monoglycerides (E471), ...
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Euphorbiaceae
Euphorbiaceae, the spurge family, is a large family of flowering plants. In English, they are also commonly called euphorbias, which is also the name of a genus in the family. Most spurges, such as ''Euphorbia paralias'', are herbs, but some, especially in the tropics, are shrubs or trees, such as ''Hevea brasiliensis''. Some, such as ''Euphorbia canariensis'', are succulent and resemble cacti because of convergent evolution. This family has a cosmopolitan global distribution. The greatest diversity of species is in the tropics, however, the Euphorbiaceae also have many species in nontropical areas of all continents except Antarctica. Description The leaves are alternate, seldom opposite, with stipules. They are mainly simple, but where compound, are always palmate, never pinnate. Stipules may be reduced to hairs, glands, or spines, or in succulent species are sometimes absent. The plants can be monoecious or dioecious. The radially symmetrical flowers are unisexual, w ...
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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 threonine amino acid residues on these proteins, or a member of this family. PKC enzymes in turn are activated by signals such as increases in the concentration of diacylglycerol (DAG) or calcium ions (Ca2+). Hence PKC enzymes play important roles in several signal transduction cascades. In biochemistry, the PKC family consists of fifteen isozymes in humans. They are divided into three subfamilies, based on their second messenger requirements: conventional (or classical), novel, and atypical. Conventional (c)PKCs contain the isoforms α, βI, βII, and γ. These require Ca2+, DAG, and a phospholipid such as phosphatidylserine for activation. Novel (n)PKCs include the δ, ε, η, and θ isoforms, and require DAG, but do not require Ca2+ for ...
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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 tiglium''. The structure of phorbol was determined in 1967. 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 and potent 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 contexts such as models of carcinogenesis. History and source Phorbol is a natural product found in many plants, especially those of the Euphorbiaceae and Thymelaeaceae families. Phorbol is the a ...
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