Tumor-promoting diterpenes

A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed to detect tumor-promoting diterpene esters of the tigliane and ingenane types within plant extracts. Fractionation on a Cig HPLC column was followed by MS-MS-multiple reaction monitoring (MRM). 

Vogg, G. Achatz, A. Kettrap, A. Sandermann, A., Jr. Fast, sensitive and selective liquid chromatographic-tandem mass spectrometric determination of tumor-promoting diterpene esters. J. Chromatogr. A, 1999, 855, 563 573. 

Keller, R., Reist R., Adolf, W., Opferkuch, H. J., Schmidt, R., and Hecker, E. (1982). Tumor promoting diterpene esters prevent macrophage activation and suppress macrophage tumori-cidal capacity, p. Cell Biol. 50 121-134. 

Long-chain ester derivatives of phorbol, a tetracyclic diterpene from the seed oil of Croton tiglium L., including its most abundant representative, 12-0-tetradecanoylphorbol-13-acetate (65), are potent activators of protein kinase G (PKG) and are used as standard tumor promoters for the study of experimental carcinogenesis in animal models." ... 

Croton f lavens. Analysis of the leaf extract shows the presence of diterpene di- and triesters that are structurally related to TPA (49). The diesters exhibit strong tumor promoting activity in dorsal mouse skin. Each cup of tea contains more tumor promoter than is required to maintain chronic irritation of the human esophagus, a necessary requirement for the promotion of esophageal cancer. 

Tetradecanoylphorbol 13-acetate (TPA) and other diterpene esters from the plant family Euphorbiaceae are well-known as tumor-promotion agents [85]. Thus, inhibition of the biological effects induced by TPA has been considered as a promising strategy [68]. To date, two short-term cell-based in vitro bioassays using TPA as a tumor-promoter have been developed to evaluate the potential cancer chemopreventive activities of several lignans isolated from Hernandia species, namely, inhibition of Epstein-Barr virus early antigen activation [6] and the inhibition of the transformation of JB6 mouse epidermal cells [7]. 

Goerttler, K., Loehrke, H., Schweizer, J. and Hesse, B. 1982, Diterpene ester-mediated two-stage carcinogenesis, Jn "Carcinogenesis, Vol 7, Cocarcinogens and Biological Effects of Tumor-Promoters", E. Hecker, N.E. Fusenig, W. Kunz, F. Marks and H.W. Thielmann, eds.. Raven Press, New York. 

A) The manganas (apples) or manganillas (little apples), from which the poison was made, came from the ill-reputed machineel tree, Hippomane mancinella L. (Euphorbiaceae). Especially noteworthy is the attempt by Enciso to determine the effects of the poison—it is probably one of the earliest experiments reported in the literature that may properly be termed pharmacological. The unpleasant nature of the plant is due to the presence in its latex of a complex mixture of potent pro-inflammatory and tumor-promoting esters of various diterpene alcohols (20, 21). 

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