Anti-neoplastic effect

Other papers in the Symposium deal with the antioxidant and hypolipidemic effects of IP6, its chelating effects in heavy metal toxicity, inhibition of renal stones and other beneficial effects such as inhibition of platelet aggregation, inhibition of inflammatory responses (Shamsuddin, 1998). The lipid lowering effect and anti-neoplastic effect of 1P6 were extensively reviewed (Jariwalla, 1999). Hence, 1P6 is a valuable component of rice bran in preventing disease and maintaining health. 1P6 is present at 1.8-2% in rice bran. 

Ideally, future antineoplastic drug discovery should be based on a more rational, botanical, chemical, and pharmacological approach. A possible way to test the anti-neoplastic effects of compounds would be to use some semi in vitro-in vivo models. A more rational approach in antineoplastic research, combined with the enormous chemodiversity of flowering plants, will lead to the discovery of several molecules of clinical value. 

Since guanine aminohydrolase catalyzes the deamination of thioguanine and 8-azaguanine thereby destroying their anti-neoplastic effects, Baker and his colleagues have prepared a series of active site directed irreversible inhibitors to block the enzyme in tumor tissue (193). The most effective inhibitor, 9-(4-methoxy phenyl)guanine, effected a 50 inhibition at 0.38 nM in the presence of 13.3 juM substrate (194). 

Jin Wong, H., Kyoungttwa, L. and Jim, E.S. (1 994) Anti neoplastic effects of extracts from tradition medicinal plants. Korean Journal of Pharmacognosy, 25, 1 71-1 77. 

Nishino, H., Tsushima, M., Matsuno, T., Tanaka, Y., Okuzmi, J., Murakoshi, M., Satomi, Y., Takayasu, J., Tokuda, H., Nishino, A., and Iwashima, A. 1992. Anti-neoplastic effect of halocynthiaxanthin, ametabolite of fucoxanthin. Anticancer Drugs, 3, 493 197. 

Diethyltin-A-(2-pyridylmetylene)-4-toluidine dichloride was tested against P338 leukemia in mice and showed anti-neoplastic effects. This compound has induced significant delay in cell cycles in mouse bone marrow cells. 

A recent example of a pro-apoptotic benzofurazan GST inhibitor, and potential anti-cancer agent, is BF.2 (Turella et al. 2005). Although it has been speculated that furazans are oxidized to furoxans in vivo, there is little evidence that furazan activity is caused by NO release. However, both furazans and furoxans are thiophilic and it is likely that these warheads share NO-independent anti-neoplastic effects through modification of biological thiols, a mechanism speculated on in 1992 (Feelisch et al. 1992). 

Additive bone marrow depressive effects occur when the miotic inhibitor drugs are administered with other anti-neoplastic dragp or radiation therapy. Administration of vincristine with digoxin results in a decreased therapeutic effect of tlie digoxin and decreased plasma digoxin levels. There is a decrease in serum concentrations of phenytoin when administered widi vinblastine... 

In terms of pharmacokinetics, many host factors, such as the route of administration, the metabolism, the catabolism and clearance will considerably determine the anti neoplastic success of a drug. One major difficulty with the clinical effectiveness of chemotherapy of neoplastic diseases is the requirement that it kill malignant tumor cells at doses that allow cells in the patient s vital organs to survive so that the recovery can occur. In other words, it is to obtain a reasonably safe therapeutic index favoring introduction into clinical practice. 

In contrast to the effects of secondary bile acids like DCA, UDCA, which is found at a high concentration in bear bile but only in trace amounts in humans, has anti-neoplastic activity in vitro and in vivo. UDCA has significant chemopreventative activity in rodent models of sporadic and colitis-colorectal carcinogenesis induced by chemical carcinogens. 

The mechanistic basis of the anti-neoplastic activity of UDCA and the explanation for the significant difference in bioactivity of UDCA compared with DCA despite marked similarity in chemical structure remain unresolved. UDCA administration in healthy volunteers and colorectal adenoma patients has been demonstrated to decrease the proportion of DCA in aqueous phase stool. Therefore, one possible mechanism of the chemopreventative activity of UDCA is reduction of mucosal secondary bile acid exposure. Consistent with this idea, UDCA administration has been demonstrated to reduce the incidence of K-ras mutations and decrease Cox-2 expression in AOM-induced tumors, which is the opposite of the reported effects of DCA in the same model. However, it is clear that exogenous administration of UDCA has direct anti-neoplastic activity on human CRC cells in vitro, either alone or in combination with DCA, including anti-proliferative and anti-apoptotic effects, as well as induction of cell senescence. " ... 

Phenanthrenebiguanides possess 384) some activity against cancer. The effect of biguanides on plasma protein surface has been investigated 294, 610) with a view to the possibility of finding anti-tumor ents. Aryl-and naphthyl-biguanides exhibit 625) a slight anti-neoplastic activity in vitro in Ehrlich ascites carcinoma. 

Anthelmintic, antiprotozoal, anti-neoplastic, and antiviral agent Binds many proteins, i.e., cytokines. epidermal growth factor, and members of the FGF family inhibits dengue virus infec-tivity of host cells very long in vivo half-life, exhibits a wide range of toxic side effects 40-47... 

B. Amaez, A. Alfonso, M. Estevez, et al. Effect of purification, theophylline and sodium fluoride on histamine release produced by anti neoplastic drugs on rat mast cells, A distinctive mechanism of action forcarboplatiiL Biochem. Pharmacol 44 533 (1992). 

Aza-enediynes are a new class of anti-neoplastic agents that produce a cytotoxic effect through an aza-Bergman cyclization (1) of an enediyne core to a 1,4-didehydrobenzene reaction intermediate. Both Bergman and benzothiazolium salt diradical cyclizations are illustrated in Eq. 1 and Eq. 2, respectively. 

In vitro studies have shown that vanadyl very effectively cleaves DNA in the presence of peroxide. Apart from the possible beneficial effect of this process in anti-neoplastic activity, toxic effects pertinent to vanadium -damage of DNA of healthy cells — has to be taken into account. 

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