Cancer and apoptosis

Apoptosis and Cancer Chemotherapy, edited by John A. Hickman and Caroline Dive, 1999... 

Sellers WR, Eisher DE. Apoptosis and cancer drug targeting. J. Clin. Invest. 1999 104 1655-1661. 

Debatin, K. M., Fulda, S. (Eds.). 200C). Apoptosis and Cancer Therapy. Wiley-VCH Verlag GmbH Co. KGaA. 

The growing knowledge about the close connection between apoptosis and cancer has led to an explosion of research revolving around apoptotic induction with chemotherapeutic agents and small molecule inhibitors. 

One of the most important properties of chitosan is its antitumor activities for cancer therapy. Chitosan is reported to cause apoptosis and cancer cell cytotoxicity through caspase-3 activation. This property has been demonstrated on different tumor cells such as bladder, breast and colon cancer cells in different studies. Chitosan also has immunoadjuvant effects. It has been shown to stimulate macrophages and polymorphonuclear cells, thus inhibiting tumor cell proliferation. Thanks to these properties, chitosan has been extensively studied as a polymer for nanocarriers for decades. 

P-53 is an important phosphoprotein, mw = 53,000, which has been linked with apoptosis and cancer, and is a type of tumor-supressor gene (Chapter 12.13). 

Hickman JA, Potten CS, Merritt AJ, Fisher TC (1994) Apoptosis and cancer chemotherapy. Philos Trans R Soc Lond B BiolSci 345 319-325... 

Simoni D, Tolomeo M (2001) Retinoids, apoptosis and cancer. Curr Pharm Des 7 1823... 

Moscat J, Diaz-Meco MT. (2009) p62 at the crossroads of autophagy, apoptosis, and cancer. Cell 137(6), 1001-1004. 

A. K. Panigrahi and D. Pati, Road to the crossroads of life and death linking sister chromatid cohesion and separation to aneuploidy, apoptosis and cancer, Crit. Rev. Oncol. Hematol., 2009, 72, 181 193. 

The double edged sword effect of Cd ", namely apoptosis and cancer progression, is reflected in its opposing effects on p53. Cd " inhibits DNA base excision repair in p53-dependent and -independent manners [593], increases p53 phosphorylation as a prelude to apoptosis [594,595], and arrests cells in G1 and G2/M checkpoints via p53-dependent [510] and -independent [596] mechanisms. Cd " can affect p53 in two ways p53 is activated by phosphorylation via phosphatidylinositol-3-kinase related kinases [479] or Cd replaces zinc to maintain its mutated non-DNA binding form preventing apoptosis induction [597]. 

Besides direct apoptosis effectors, there are a number of other diugs which influence the above explained apoptosis pathways more indirectly. This class of diugs includes molecules which inhibit survival pathways like e.g. the Ras/Raf kinase pathway, the NF-kB pathway and many others. Also inhibitors of survival cytokines which are sometimes produced by cancer cells in an autocrine fashion can render cells susceptible to apoptosis and, hence, effective cancer therapy. These include, but are not limited to, ligands for dependence receptors and cytokines like e.g. interleukin-4. 

Ras is a G protein that cycle between two conformations, an activated Ras-GTP or inactivated form Ras-GDP. Ras, attached to the cell membrane by lipidation, is a key component in many signalling cascades, which couple growth factor receptors to downstream effectors that control such processes as cytoskeletal integrity, proliferation, cell adhesion, apoptosis and cell migration. Mutations and dysregulations of the Ras protein leading to increased invasion and metastasis, and decreased apoptosis are very common in cancers. 

Ohnishi H, Asamoto M, Tujimura K, Hokaiwado N, Takahashi S, Ogawa K, et al. Inhibition of cell proliferation by nobiletin, a dietary phytochemical, associated with apoptosis and characteristic gene expression, but lack of effect on early rat hepatocarcinogenesis in vivo. Cancer Sci 2004 95 936-42. 

Bcl-2 is one of the many factors that control apoptosis, and overexpression of Bcl-2 has been observed in many different cancers. A homology model of Bcl-2 was derived from the NMR 3D structure of the Bcl-XL complex with a Bak BH3 peptide. This model served to search the NCI 3D database of 206,876 organic compounds for potential Bcl-2 inhibitors, which bind to the Bak BH3 binding site of Bcl-2. Full conformational flexibility of the ligands was taken into account in the program DOCK. Thirty-five potential inhibitors were tested, and seven of them had IC50 values from 1.6 to W.OpM. One of... 

YU R, mandlekar s, HARVEY K J, UCKER D s and KONG A N (1998) Chemopreveutive isothiocyanates induce apoptosis and caspase-3-like protease activity . Cancer Res, 58 402-8. 

SALTI G I, GREWAL S, MEHTA R R, DAS GUPTA T K, BODDIE A W, CONSTANTINOU A I (2000) Genistein induces apoptosis and topisomerase Il-mediated DNA breakage in colon cancer c lli. Eur J Cancer. 36 796-802. 

ZHOU J R, MUKHERJEE P, GUGGER E T, TANAKA T, BLACKBURN G L, CLINTON S K (1998) Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis and angiogenesis. Cancer. Res. 58 5231-8. 

Tocotrienols are another group of phytochemicals of rice bran which have a chemopreventive effect and have been demonstrated to inhibit breast cancer (Nesaremam et al., 1998). The polysaccharides of rice bran contain a-glucan, the anti-tumor effect of which has been demonstrated by its inhibition of gastrointestinal carcinogenesis (Akeshita et al., 1992). Rice bran agglutinin has been shown to induce apoptosis of cancer cells by the mechanism of cell cycle dysregulation (Miyoshi et al., 2001). 

Different types of apparently beneficial activities have been demonstrated in vitro for carotenoid oxidation products, including induction of gap-junctional communications, " growth inhibition of leukemia and cancer cells, induction of apoptosis... 

Additional genes and protein receptors are believed to be important in colorectal tumorigenesis. Cyclooxygenase 2 (COX-2), which is induced in colorectal cancer cells, influences apoptosis and other cellular functions in colon cells, and overexpression of the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein involved... 

Thus, expression of CXCR4 on tumor cells, which is common to many breast cancers as well as other cancer types, may contribute to malignant behavior in several ways. CXCR4 expression by tumor cells may interact with CXCL12 to facilitate tumor cell growth and escape from oxygen starvation-induced apoptosis and as a mechanism to home (metastasize) to secondary sites. 

Carotenoids can strongly modulate apoptotic pathways (Palozza et al., 2006). For example, it has been demonstrated that lutein and zeaxanthin modulate the expression of anti-and pro-apoptotic factors and can selectively induce apoptosis in cancer cells but not in normal cells (Chew et al., 2003 Maccarrone et al., 2005). 

Cui, Y., Lu, Z., Bai, L., Shi, Z., Zhao, W.E., and Zhao, B. 2007. Beta-carotene induces apoptosis and up-regulates peroxisome proliferator-activated receptor gamma expression and reactive oxygen species production in MCF-7 cancer cells. EurJ Cancer 43 2590-2601. 

Hosokawa, M., Kudo, M., Maeda, H., Kohno, H., Tanaka, T., and Miyashita, K. 2004. Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARgamma ligand, troglitazone, on colon cancer cells. Biochim Biophys Acta 1675 113-119. 

Bonnesen C, Eggleston I M and Hayes J D (2001), Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines , Cancer Rese, 61, 6120-6130. 

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