Recently, the modulation of cellular signaling pathways by naturally occurring phytochemicals has been used to explain the molecular basis of cancer chemoprevention with dietary factors. Dietary chemo-preventive agents are derived from the fruits, vegetables, tea, coffee, and beverages consumed daily by people.
Due to the fact that the incidence of cancer remains high all over the world, the concept of cancer intervention by means of those dietary phytochemicals needs to be more widely spread and accepted. As we have a better understanding of the genetic and epigenetic mechanisms of carcinogenesis at the level of signal transduction, additional molecular targets have been and will be identified for the potential intervention at the initiation, promotion and progression stages during carcinogenesis and cancer development.
So far, these molecular targets include transcription factors such as Nrt2, NF-κB, AP-1 and MAPKs. The signaling pathways mediated by these transcription factors in response to pro-inflammatory cytokines, growth factors, xenobiotics, oxidative stress and tumor promoters can adjust a wide arrangement of genes involved in many cellular events such as cell-cycle control, differentiation, transformation, apoptosis and carcinogenesis. Because of their potential role in preventing cancer from developing, the mechanisms by which phytochemicals regulate signaling pathways have been expanded and developed.
As an example, dietary chemo-preventive agents activate Nrf2-mediated gene expression either by directly modifying the cysteine residues on Keap1 to disrupt the Nrf2-Keap1 complex or by activating kinase signaling pathways such as MAPKs, protein kinase C (PKC), and PI3K to phosphorylate Nrf2/Keap1 complex and/or facilitate the release of Nrf2 or to increase the nuclear translocation of Nrf2 and regulate the transcriptional activity of Nrf2 nuclear c0-activators. While many chemo-preventive agents directly act on the Nrf2/ARE signaling pathway to induce detoxification and antioxidant enzyme systems, which may block tumor initiation in normal cells, the same compounds and/or others may exert anti-promotion or anti-progression effects by modulating the NF-κB and AP-1 signaling pathways in abnormal pre-initiated cancer cells. Cellular signaling cascades mediated by NF-κB and AP-1 generally act as key regulators of many of the aforementioned biochemical processes. Results from both in vitro and in vivo studies suggest that phytochemicals can inhibit the activation of NF-κB and/or AP-1 in a cell-or tissue-specific manner. Although experimental data from cell culture models provide valuable information regarding the molecular and cellular mechanisms, the signal transduction cascades between the interplay of phytochemicals and transcription factors are still not fully understood. For instance, although NF-κB and AP-1 may be considered as prime molecular targets for chemoprevention by dietary phytochemicals, cell type- and stimuli-dependency between these two transcription factors often makes it complied to deduce a unique mechanism for the chemo-preventive activity of phytochemicals.
While chemoprevention studies using animal models certainly provide promising results for the chemo-preventive agents discussed above, future confirmatory human clinical trials coupled with epidemiological data would be needed to support their eventual chemo-preventive potentials. The modulation of the above signaling pathways, transcription factors and genes expression by cancer chemo-preventive phytochemicals would provide potential opportunities for future design of chemo-preventive agents based on molecular targeting.
About Stanford Chemicals http://www.bestherbalextract.com/
Stanford Chemicals is a worldwide supplier of phytochemicals, pharmaceutical intermediates, catalysts, lab equipment and a variety of special fine chemical products since 1994. To meet increasing demands for herbal extracts in nutraceutical, pharmaceutical and cosmetic industries, Stanford Chemicals is established and now carries hundreds kinds of herbal extracts, including botanical ingredients and standard herbal extracts.
Stanford Chemicals 