viernes, 10 de febrero de 2017

Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?

Resultado de imagen de celulas cancerigenas

There are four types of cancers; (a) carcinoma: arise from the epithelial sheet that covers the surfaces, e.g., skin, colon, etc. Approximately 90% of all human cancers are carcinomas; (b) sarcoma: these include cancer of the connective tissues such as muscle, bone, cartilage, and fibrous tissue. Approximately 2% of all cancers are sarcomas; (c) leukemia and (d) lymphoma: they originate from blood forming cells and from cells of the immune system, respectively. Approx. 8% of all cancers are leukemia and lymphomas. Based on metastatic potential, there are two classifications of cancers; (a) benign tumors or adenomas: when neoplastic growth remains clustered as a single mass, (b) malignant tumor or adenocarcinoma: when tumor invades normal tissue and spreads throughout the body. 

It is estimated that human body consists of 10–13 trillion cells. Almost all of these cells get turned over within approximately 100 days, thus suggesting an apoptosis/cell death rate of 100–130 billion cells each day. What is the mechanism of this mode of cell death in normal cells is unclear. Cancer cells are distinct from normal cells in six different ways and these characteristics are shared by all cancers; self sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion, and metastasis (1). The ability of tumor cell populations to expand in number is determined not only by the rate of cell proliferation but also by the rate of cell death. Apoptosis is a major source of cell death, thus agents that trigger apoptosis/ cell death, could be the most promising candidates as therapeutic for cancer. Why certain types of cancers are more prevalent in some countries than others is not clear but lifestyle, including diet, is known to play major role (2). Among the potential dietary contributors to this disparity is turmeric (Curcuma longa), a spice that is consumed frequently by people from southeast Asia, a continent with low incidence of most cancers. Powder of turmeric is extensively used in Ayurveda, Unani, and Siddha medicine as a home remedy for various diseases. This powder, curcumin (diferuloylmethane) is a yellow-colored polyphenol, first isolated in 1815, crystallized in 1870, (3,4) and identified as 1,6-heptadiene-3,5- dione-1,7-bis(4-hydroxy- 3-methoxyphenyl)-(1E,6E). 

Curcumin analoges which made by mother nature and man have been described (2). In addition, besides diferuloylmethane or curcumin, turmeric contains minor fractions such as demethoxycurcumin (curcumin II), bisdemethoxycurcumin (curcumin III), and the recently identified cyclocurcumin (5).

 All these analoges suggest that while hydroxyl groups in curcumin are required for its antioxidant activity, its methoxy groups are essential for its antiinflammatory and antiproliferative activity. Various molecular targets modulated by this agent include transcriptionfactors, growth factors and their receptors, cytokines, enzymes, and genes regulating cell proliferation and apoptosis (6) The anticarcinogenic properties of curcumin in animals have been demonstrated by its inhibition of tumor initiation (7) and tumor promotion (8,9). Studies of curcumin have shown that it influences structurally unrelated membrane proteins across several signaling pathways (10). A recent report suggests that curcumin inserts deep into the cellular membrane in a transbilayer orientation, anchored by hydrogen bonding to the phosphate group of lipids, thus inducing negative curvature in the bilayer (11). The promotion of negative curvature by curcumin may have a direct effect on apoptosis by increasing the permeabilizing activity of the apoptotic protein tBid (12). Curcumin has been shown to suppress multiple signaling pathways and inhibit cell proliferation, invasion, metastasis, and angiogenesis. The chemopreventive action of curcumin might be due to its ability to induce apoptosis by several pathways. Curcumin directly or indirectly controls different gene or gene products involved in cell death pathways as discussed here swelling, plasma membrane rupture, organelle breakdown, and ultimately lysis, allowing release of the cytoplasmic contents and hence induction of an inflammatory response.
Referencia: /Curcumin%202009.pdf

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