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    S containing bioactive cancer preventive compounds in almost all major genera and in every class of primary and secondary metabolites of Euphorbiaceae.
    By Ashwani Kumar | November 7th 2009 08:12 PM | Print | E-mail | Track Comments
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    Professor Emeritus ,Former Head of the Department of Botany, and Director Life Sciences, University of Rajasthan, Jaipur. 302004, India At present...

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    S containing bioactive cancer preventive compounds in almost all major genera and in every class of primary and secondary metabolites of Euphorbiaceae. The glucosinolates are especially abundant among families of the order Capparales: Tovariaceae, Resedaceae, Capparaceae, Moringaceae, and Brassicaceae. Families outside the order exhibit occasional occurrence and include the Caricaceae, Euphorbiaceae, Gyrotemonaceae, Limnathaceae, Salvadoraceae, and Tropaeolaceae (Fenwick et al. 1983). A recent literature review provides a comprehensive list of all species known to contain glucosinolates (Fahey et al. 2001). In Euphorbiaceae it is abundant in the Genus Drypetes, and apparently no other genera of this family is said to have these compounds (Rodman 98). As far as the bioactive cancer preventive compound are concerned there are lot of them in different classes of secondary metabolites of family Euphorbiaceae and are studied a lot for their anti cancer activities in recent years but any of them containing sulfur is so far not discovered. I have searched extensively in various classes viz; sulfonated oxime groups, thiones, allyl isothiocynates, thioglucosides, thiohydroxy-o-sulphonates, thiosulphinates, sulfated terpenoids, sulfated flavonoids, sulfated alkaloids, sulfoxides, sulphahydryl groups, sulphated polysaccharides, sulphoraphans, thio recidues and vinyl thiooxazolidines besides many more. Since most of the S containing compounds are either primary metabolites or are the result of such metabolism, coming from amino acids or proteins and hence not supposed to be present in the secondary metabolites; glucosinolates are the exceptional secondary metabolites containing S moiety. Though sulfated terpenoids, polysaccharides etc are abundant in this family and sulphation of flavonoids is well known, but most of this S is inorganically present and I personally believe that such incorporation is of no use for compound’s bioactivity against any diseases since this seems either for the excretion purpose or for translocation of the sulfur moiety from one place to other or from one molecule to other. Among all these the flavonoids are the most promising bioactive compounds having anti cancer properties but again no known flavonoid is present in the plants having organic S moiety. Vinyl thiooxazolidine, which is according to some reports present in J. curcas is used in paint industry and not studied for its bioactivity, if present at all. One another compound seems to contain S is mapourinic acid that is a terpenoid present in some members of Euphorbiaceae is again not known for any cancer preventive activity though have anti-HIV properties. I am not sure that this contains S or not because as such I could not find out its chemical structure in any literature or at Internet in any chemical database. Drypetes is a genus of family Euphorbiaceae and exceptionally has glucosinolates and is pan-tropical in its distribution. The Genus is probably of Indo-Malayan in origin & naturally grows at many geographical areas and abundantly present at Australia, Malaysia, Indonesia, Philippines, Nigeria and some other African countries and Indian sub continent besides UK and other parts of Europe, Costa Rica and US. We find its description at herbarium of Central Queens land University, Australia and at herbarium of Kew. In Nigeria, Country Report has been prepared by the national authorities in the context of the preparatory process for the FAO International Technical Conference on Plant Genetic Resources, Leipzig, Germany, June 17-23 1996, and declared Drypetes gossweileri as endangered species. At Costa Rica a frequently occurring species at costs is Drypetes glauca commonly called as Asolillo/ Sardinillo. In Nepal another species D. roxburghii is present; which somehow show its migration from some costal area to this place. In Australia it is widely cultivated in gardens and nurseries and one of the nursery named Yuruga at Walkamin, Atherton Tablelands, Australia cultivates and maintains Drypetes acuminata, Drypetes deplanchei, Drypetes idoformis, Drypetes lasiogyna and Drypetes vernicosa. Some of its species are edible. Drypetes longifolia (locally called Opodon putih) is indigenous edible plant of SABAH (Malaysia), ripe fruit is sweet and eaten raw. Likewise D.deplanchei is also edible and ripe fruits and leaves are eaten raw. National Herbarium Nederland in February 1997 published following 72 species of Dyrpetes and their geographical location in Malaysian Euphorbiaceae newsletter volume 6, however it is not quoted how many of them are edible. Name Of Species Geographical Location Drypetes aetoxyloides Borneo Drypetes assamica Thailand Drypetes australasica New Guinea Drypetes bawanii Philippines Drypetes caesia Borneo Drypetes calyptosepala Sumatra Drypetes cambodica Thailand Drypetes castilloii Borneo Drypetes celebica Philippines Sulawesi (Celebes) New Guinea Drypetes cockburnii Malay Peninsula Drypetes convoluta Philippines Drypetes crassipes Sumatra Borneo Drypetes cumingii Philippines Lesser Sunda Islands Drypetes curtisii Thailand Malay Peninsula Borneo Drypetes dasyneura Sumatra Drypetes detersibilis Malay Peninsula Drypetes dewildei Sumatra Drypetes ellipsoidea Philippines Drypetes eriocarpa Borneo Drypetes falcata Philippines Drypetes forbesii Sumatra Drypetes fusiformis Borneo Drypetes gitingensis Philippines Drypetes glaberrima New Guinea Drypetes globosa Philippines Drypetes grandifolia Philippines Drypetes hainanensis Thailand Borneo Drypetes harmandii Thailand Drypetes helferi Thailand Drypetes heptandra Philippines Drypetes hoaensis Thailand Drypetes impressinervis Borneo Drypetes indica Thailand Malay Peninsula Drypetes kikir Malay Peninsula Borneo Drypetes laevis Malay Peninsula Sumatra Drypetes lasiogyna Lesser Sunda Islands Drypetes littoralis Borneo Philippines Sulawesi (Celebes) Lesser Sunda Islands Drypetes longifolia Thailand Malay Peninsula Sumatra J Borneo Philippines Sulawesi (Celebes) Moluccas Lesser Sunda Islands New Guinea Drypetes lysiogynoides New Guinea Drypetes macrophylla Java Drypetes macrostigma Sumatra Borneo Drypetes maquilingensis Borneo Philippines Sulawesi (Celebes) Moluccas Lesser Sunda Islands Drypetes megacarpa Borneo Drypetes microphylla Malay Peninsula Borneo Philippines Drypetes microphylloides Sumatra Drypetes minahassae Java Drypetes mindanaensis Philippines Drypetes monosperma Philippines Drypetes neglecta Java Borneo Sulawesi (Celebes) Lesser Sunda Islands New Guinea Drypetes nervosa Malay Peninsula Drypetes ochrodasya Sumatra Drypetes ochrothrix Thailand Borneo Drypetes ovalis Java Philippines Sulawesi (Celebes) Lesser Sunda Islands Drypetes oxyodonta Malay Peninsula Drypetes pendula Thailand Malay Peninsula Borneo Drypetes perakensis Malay Peninsula Drypetes perreticulata Thailand Drypetes polyalthioides Borneo Drypetes polyneura Sumatra Borneo Drypetes prunifera Borneo Drypetes rhakodiskus Malay Peninsula Sumatra Java Borneo Philippines Drypetes rheophila Borneo Drypetes riparia Malay Peninsula Drypetes roxburghii Thailand Sumatra Java Borneo Sulawesi (Celebes) Moluccas Lesser Sunda Islands New Guinea Drypetes serrata Java Drypetes sibuyanensis Sumatra Borneo Philippines Sulawesi (Celebes) Drypetes simalurensis Sumatra Drypetes stylosa Borneo Drypetes subcrenata Philippines Drypetes subcubica Java Lesser Sunda Islands New Guinea Drypetes subsessilis Thailand Drypetes sumatrana Sumatra Lesser Sunda Islands Besides this the other species of the genus are as follows but again it is not certain that how many of them are edible. Drypetes brownii, Drypetes globosum, Drypetes glossweileri, Drypetes hainanensis, Drypetes lateriflora, Drypetes longifolia, Drypetes neglecta, Drypetes ovalis, Drypetes sibuyanensis, Drypetes simularensis, Drypetes subcubica, Drypetes subsymmetrica, Drypetes variabilis. Following species are reported to occur in Kerela, India as well and I presume that other species must be occurring in same geographical climate elsewhere in world. • Drypetes confertifolia • D. elata • D.malabarica • D. oblongifolia • D. roxburghii • D. sepiaria • D. venusta and • D. wightii. But there is almost no work so far has been done on the Genus Drypetes for its glucosinolates and most of it is for the phylogenetic relationship of this group to the other groups containing glucosinolates. Specifically this is not known what types of Glucosinolates are present in this plant and what could be their probable significance against Cancer. Ergo there is handful of work to be carried out on this genus of Euphorbiaceae. In the recent years there is a whole world of work done for the glucosinolates from Crucifereae with every aspect of these. The Arabidopsis, which is a plant of Brasiccaceae here again worked as a model plant as in many researches earlier and even QLTs have been studied in it and in B. napus. The glucosinolates themselves posses a wide diversity with different facets and bioactive capabilities and so is the cancer having its different types and tissues of occurrence. Mechanism of induction of tumour cell apoptosis by dietary isothiocyanates: 1. Entry of the isothiocyanate into cells and formation of the GSH conjugate, S-(N-alkyl or aralkyl thiocarbamoyl)glutathione. Concurrently, there is a slow inactivation of PEITC by spontaneous hydrolysis. 2. Expulsion of the GSH conjugate via the MRP protein channel, with a consequent depletion of cellular GSH. 3. A temporary, reversible modification of cellular protein thiols – protein thiocarbamoylation. 4. Event 3 triggers recruitment of adaptor protein FADD to apoptosis-mediating cell death receptors (tumour necrosis receptor 1 and/or the fas receptor) and activates caspase-8. 5. Cleavage of mitochondrial protein BID, release of cytochrome c from mitochondria and activation of caspase-3. Activation of the stress activation protein kinase JNK (which induces increased expression of the fas receptor ligand – further potentiating apoptosis) via activation of the mitogen activated kinase kinase kinase MEKK1 and the mitogen activated kinase kinase SEK1. 6. Induction of apoptosis, DNA fragmentation and cell death. Where the isothiocyanate (RN=C=S) is administered as the corresponding thiol conjugate (RNH(C=S)-SR'), this sequence of events is preceded by fragmentation of the thiol conjugate to the free isothiocyanate. Thornalley, P.J. (2002) Isothiocyanates: mechanism of cancer chemopreventive action. Anticancer drugs 13, 331-338. Glucosinolates are amino acid-derived natural plant products found throughout the Capparales order. Glucosinolates and their degradation products have a wide range of biological activities, e.g. in plant defense as deterrents against insect and fungi. The conversion of amino acids to aldoximes is a key step in glucosinolate biosynthesis. This step is catalyzed by cytochromes P450 from the CYP79 family. The post-aldoxime enzymes in the glucosinolate pathway have high substrate-specificity for the functional group and low substrate-specificity for the side chain. Therefore, we have been able to metabolically engineer new glucosinolate profiles into Arabidopsis by altering the levels of endogenous CYP79s and by introducing exogenous CYP79s. The approach has great potential for design of metabolically engineered plants with improved pest resistance and increased nutritional value, writes M. D. Mikkelsen, B. L. Petersen, C. E. Olsen, and B. A. Halkier of The Royal Veterinary and Agricultural University, Frederiksberg C, Copenhagen, Denmark. The above description suggests that the Genus is having both the food plants as well as glucosinolates in its members hence this could be considered for neutraceuticular studies besides members of Capparales, the later being almost studied well (even QLTs are affixed in Arabidopsis and B. napus) and so having probably a little potential for new research but this genus seems certainly promising as there is no research so far and I am sure this would not be a hyperbole if some of the species which are not yet eaten can be promoted as new food crops if they are better over others; qualitatively or quantitatively in glucosinolates contents. Even, if possible some of the non-edible species can be used to improve the edible ones for DESIRED EFFECTS by different breeding methods; once they are proved SUPERIOR. Secondly some of the chosen compounds once establishing their role very well can be used directly into tailoring drugs against the specific type of cancer.