Cancer cells promoters

The water-soluble compound 36b, very stable within a physiological buffer at 37 ° C, exhibits cytotoxic effects on ovarian A2780 human cancer cells and promotes apoptosis to a greater extent than platinum drugs [103]. 

Helbig G, Christopherson KW, Bhat-Nakshatri P, et al. NF-kB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J Biol Chem 2003 278 21631-21638. 

Kimsey TF, Campbell AS, Albo D, Wang TN. Co-localization of macrophage inflammatory protein-3a (Mip-3a) and its receptor, CCR6, promotes pancreatic cancer cell invasion. Cancer J 2004 10 374-380. 

King-Batoon et al. have found that the physiological concentrations of lycopene (2pM) partially demethylated the promoter for GSTP1 and restored its expression in the breast cancer cell line MDA-MB-468, but RAR0 was not demethylated. However, lycopene did induce the demethylation of RARp in MCF10A fibrocystic cells (King-Batoon et al. 2008). Genistein, in this study, was less active compared to lycopene. 

Brognard, J., Clark, A.S., Ni, Y., and Dennis. P.A. 2001. Akt/protein kinase b is constitutively active in nonsmall cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. 

Clark, A.S., West, K., Streicher, S., and Dennis, P.A. 2002. Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells Mol Cancer Ther 1 707-717. 

In addition to their possible prooxidant activity (see above) polyphenols and flavonoids may influence cancer cells via their antioxidant properties. Recently, Jang et al. [219] studied cancer chemopreventive activity of resveratrol, a natural polyphenolic compound derived from grapes (Chapter 29). These authors showed that resveratrol inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. Flavonoids silymarin and silibinin also exhibited antitumor-promoting effects at the stage I tumor promotion in mouse skin [220] and manifested antiproliferative effects in rat prostate cancer cells [221]. 

Initial classification of some cytokines was also undertaken on the basis of the specific biological activity by which the cytokine was first discovered (e.g. TNF exhibited cytotoxic effects on some cancer cell lines CSFs promoted the growth in vitro of various leukocytes in clumps or colonies). This, too, proved an unsatisfactory classification mechanism, as it was subsequently shown that most cytokines display a range of biological activities (e.g. the major biological function of TNF is believed to be as a regulator of both the immune and inflammatory response). More recently, primary sequence analysis of cytokines coupled to determination of secondary and tertiary structure reveal that most cytokines can be grouped into one of six families (Table 8.2). 

IL-6 induces terminal maturation of B cells, promotes the growth of hy-bridoma/myeloma cells and T cells, and acts upon haematopoietic progenitors in synergy with IL-1 and IL-3. It also induces the production of acute-phase proteins by liver cells. In addition to its production by neutrophils, IL-6 is also synthesised by monocytes, T and B cells, fibroblasts, cardiac myxoma cells, some bladder carcinomas, cervical cancer cells and glioblastomas. Stimulated neutrophils generate about ten times less IL-6 (on a per-cell basis) than do monocytes. 

Unlike the situation with the integrins discussed earlier, it is loss of cadherin E that promotes metastasis. The evidence linking loss or decreased expression of cadherin E with cancer spread is as follows (M2). Firstly, a negative correlation exists between the expression of cadherin E and invasion for many different cancer cell lines. Secondly, in cell lines lacking cadherin E, invasion could be prevented by transfection with cDNA for this cadherin. Thirdly, reduction in cadherin E mRNA levels by antisense sequences induced the invasive phenotype in E-cadherin positive cells. Fourthly, antibodies inactivating cadherin E induced the invasive phenotype. These combined experiments are strong evidence that loss of cadherin E is associated with development of invasive phenotype and furthermore suggests that this adhesion molecule may be a suppressor of metastasis. 

J. A. Engelman, X. L. Zhang, and M. P. Lisanti. Methylation of a CpG island in the 5 promoter region of the caveolin-1 gene in human breast cancer cell lines. FEBS Lett. 448 221-230 (1999). 

The recent findings of the localisation of nucleolin at the cell surface of cancer cells and its involvement in DNA replication have promoted the development of anti-cancer drugs targeting nucleolin and the use of nucleolin as a marker for the diagnosis of cancer. 

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