*4.2.2. Cytochrome C*

14 Apoptosis and Medicine

cell abnormal proliferation.

active components in the drug.

gastric epithelial AGS cells induced by helicobactera pylori infection. [34]. Soy isoflavone also have been documented as dietary nutrients broadly, it was been classified as "natural agents" which play the important role in reducing the incidence of hormone-related cancers in Asian countries, and have shown inhibitory effects on cancer's development and progression in vitro and in vivo. [35] Beside this soy isoflavone, in recent years, dietary compounds which was from the bounties of nature have been paid any attentions, the latest researches data have shown that there are some associations between the consumption of some native dietary compounds and the reduced risk of several types of cancers, [36, 37] because there are lots of active compounds containing in the food which have some associations with the apoptosis, and due by apoptosis, these native compounds will inhibit

Apart from these food derived natural compounds, there are many plant components which can be used by Chinese traditional medicine (TCM), these plant active components can also have trigger apoptosis, such as fisetin, wongonin, emodin and so on. Fisetin is a natural flavonoid which can induce several type cancer cells to apoptosis by dose and time dependent manner. Fisetin can activate caspase-8/caspase-3 dependent apoptosis pathway, and these pathway transducer molecular will be the candidates for cancer therapy; [38] Wongonin, as an O-methylated flavonoind, was detected to have anxiolytic activity, and also have the ability to trigger some cancer cells apoptosis. For instance, wongonin and fisetin can make PARP to be cleaved, then pro-caspase-3 will be activated in HL-60 cells, while they can induce the ROS decreased, so it is not the ROS dependent apoptosis pathway. Several compounds have the similar structural with flaconoids, including the luteolin, nobiletin, wogonin, baicalein, apigenin, myricetin and fisetin, they all have biological activities. Up to now, wogonin and fisetin have been found that they have the potential ability to trigger apoptosis through caspase-8 dependent manner[40,41]. Rheum palmatum is traditional Chinese medicines which have anti-bacteria; anti-inflammation; and improving microcirculation, emodin is an active component of Rheum palmatum and have apoptosis-inducing activity, Chen YC group found that the emodin can activate caspase-3

cascade and trigger HL-60 cell apoptosis independent of ROS production also. [41]

Some researches gave us many inspirations in the apoptosis research. We known that many tradition Chinese medicines (TCM) have some active constituents, these active components have anti-tumor activity through apoptosis, so combination the molecular biology to dig out the mechanism of drug functions will be effective and scientifical, Now, the functions of some tradition Chinese medicines are still stay the phenomena, we did not know the real mechanism of activity materials. Although TCM have not curative effect faster than western medicine, but the TCM have the lowest side effect and help for prognosis, so many patients choose TCM to defense the diseases in china. More and more investigators are focusing on elucidating the molecular mechanisms of these natural products and identifying its targets. Moreover, I think the researches of active components from TCM will be meaningful and broadly potential in the future. In the table 3, we summarized some other native compounds that can trigger apoptosis, I hope that these informations will guild us to research some Cytochrome C, as a proapoptotic protein, plays an important role in triggering programmed cell death, The activation of cytochrome C is related with the changes of Bak/Bax ratio. The latest researches shown that the interactions of heterotypic mitochondrial membrane will change the lipid milieu, in the end, mitochondrial membrane will be permeatable and cytochrome c will release. [44]; Apart the changes of lipid milieu, arachidonic acid, triiodothyronine (T3), or 6-hydroxdopamine can also effect the permeability of mitochondrial membrane and release Ca2+ and cytochrome c. [45] Cytochrome c can thrigger caspase activation via oligomerization of APAF1 protein. Caspase activation can catalyze the PARP-1, Finally, the apoptosis will happen. In short, cytochrome C is the one of major intrinsic cell apoptosis signal molecules.
