Anti-tumour-promoting activities

Vimala, S. 1999. Anti-tumour promoter activity in Malaysian ginger rhizobia used in traditional medicine. Br. J. Cancer 80 110-116. 

The synthesis and anti-tumour promoting activity of a fused 1,2,4-triazepinone derivative has also been reported by Nagai et al. [01JHC1097],... 

Brouet, I. and Ohshima, H. 1995. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem. Biophys. Res. Commun., 206 533-540. 

As endothelins mediate potent vasoconstrictor effects, ECE inhibitors and endothelin receptor antagonists were developed for the treatment of cardiovascular diseases, such as acute and chronic heart failure, pulmonary hypertension and subarachnoid haemorrhage. As ETa recqrtors have potent mitogenic responses and may promote progression of ovarian and prostate cancer and bone metastases ETA receptors are also considered as a potential targets for anti-tumour activity. 

Cytokines which can provide innate protective antiviral (e.g. interferon-a or -(3) and anti-tumour (e.g. tumour necrosis factor—TNF-a) activity against other host cells. A group of cytokines termed chemokines can also serve to chemoattract other leucocytes into an area of ongoing infection or inflammation, for example IL-8 which attracts neutrophils. Yet another group of cytokines has pro-inflammatory actions (e.g. IL-1 and TNF-a) which, among other outcomes, will lead to activation of endothelial and leucocyte cells promoting increased leucocyte extravasation into tissues and in the case of IL-1 activate T-lymphocyte populations. 

A wide range of biological activities has been described for triterpenes and nor-triterpene quinonemethides. These include anti-inflammatory, anti-hyperlipidemic, antitumour-promotion, hepatoprotective, anti-ulcer, anti-microbial and hypoglycemic activitiy, among others [16,35]. Among the compound mentioned previously in this review, antitumour-promotion, anti-inflammatory, inmunosuppressive, anti-tumour, insecticide and anti-AIDS activities were found and are described below. 

Results obtained from human prostate cell cultures and cell-free systems demonstrated inhibitory effects of palmitoleic, oleic, and myristoleic acids on the activity of human and rat microsomal 5a-reductase, which converts testosterone into 5a-dihydrotestosterone (Liang and Liao, 1992). The latter binds to androgen receptors and functions in the nucleus to regulate the expression of specific genes. 5a-Dihydrotestosterone promotes benign prostatic hyperplasia and female hirsutism. Certain 4-azasteroids are potent competitive inhibitors of 5a-dihydrotestosterone and have shown therapeutic value for treating prostate cancer. The inhibitory effect of palmitoleic acid on microsomal 5a-reductase activity may represent a mechanism related to its anti-tumour effects. 

Fig. 1 Proposed homeostatic regulation of inflammation in effective host defence. The initial phase of inflammation is initiated by a host of pro-inflammatory cytokines and eicosanoids which subsequently become diminished with time, and are coupled with the likely activation of anti-inflammatory and pro-resolution mediators, including the lipoxins, resolvins and protectins. Typically, IL 13 up-regulates 15-LO gene expression of human blood monocytes for example (Nassar et al. 1994). The associated increase in enzyme activity results in an increase in LX generation which promotes the resolution phase of inflammation. IL, interleukin TNF-a, tumour necrosis factor-a MCP-1, monocyte chemotactic protein-1 RANTES, regulated upon activation, normal T-cell expressed and secreted TGF i, transforming growth factor...

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