Role Of Gluthathione Pathway In Discovering Anticancer Compound

1121 words - 5 pages

Cancer cell have different metabolism compare to normal cell and the modification in the metabolism turn normal cell to cancer cell (Akhdar et al 2012, p.137). In the human body, anticancer drug need to pass several metabolism to change it into other form before it will distributed to the target site and will be excreted through bile or urine. There are two different phases of enzymatic system that anticancer drug will become metabolite, namely phase I and phase II (Gonzalez 2005, p. 71).

As the glutathione conjugation (phase II) plays main role in metabolism of anticancer compound, this point will be focused on. Glutathione are one of the major mechanisms controlling cellular oxidative balance (Pei et al 2013, p.2). There are three main function of glutathione (GSH) according to Pei et al (2013, p.2) :

The role of glutathione can be explained by using example of human acute myelogenous leukemia (AML) cells. By targeting the glutathione pathway, this cancer cell will be stamped out.
The primitive leukemia cells, which also known as leukemia stem cells (LSCs), are typically refractory to many forms of therapy.Research has been done to improve strategies for targeting of human AML cells by comparing the molecular mechanisms regulating oxidative state in primitive (CD34+) leukemic vs. normal specimens .By comparing this,,radox state is known as the most prevalent of the cellular properties known to differ in cancer vs.normal cell .From this,it shows that radox balance were altered .Cellular or tissue reduction-oxidation (redox) state is the result of the net balance of molecular reducing and and oxidising equivalents,and can be subdivided into intra-or extracellular redox state (inside or outside the cell),respectively.Under physiological conditions,redox state regulates cell metabolism,survival and the cell cycle (Hurren et al.2011,p.3).
Alexendra and Huang (2006 ,pp.301-311) describes that an altered redox balance has been reported for many forms of cancer, and presumably reflects a plausible therapeutic target.The result shows that CD34+ AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to recompense for increased oxidative stress in leukemic cells. Consistent from this observation, CD34+ AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared to normal CD34+ cells. Glutathione exists in both reduced (GSH) and oxidized (GSSG) states. By being in the reduced state, the thiol group of cysteine will be able to donate a reducing equivalent (H++ e−) to other unstable molecules like reactive oxygen species. Gluthathione itself becomes reactive by donating an electron, but it will readily reacts with another reactive glutathione to form glutathione disulfide (GSSG). Such a reaction is probable due to the relatively high concentration of glutathione in cells (up to 5 mM in the liver). By using enzyme gluthathione...

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