Disruption of Cellular Homeostasis
Disruption of cellular homeostasis between cell death and cell proliferation can elicit cancer (Thompsonet al., 1995). Inhibition of cell growth and induction of cell death are two major means of antitumor growth (Zhang et al., 2009). Cell cycle progression and apoptosis are two pivotal signaling mechanisms of homeostasis maintenance in healthy tissues and normal cells (Kesselet al., 2000, HU et al., 2000).The general mechanisms involved include: arrest of cell cycle in G1 phase and induction of apoptosis via the caspase-dependent intrinsic pathway.
Many anticancerous and DNA-damaging agents arrest the cell cycle at G0/G1, S or G2/M phase and then induce cell apoptosis. Most of the human solid tumors is genetically unstable and have defects in the cell-cycle checkpoint control mechanism. Such tumors frequently contain mutations that disrupt the G1 components of the cell cycle, which affects the abilities of chemotherapeutic drugs to inhibit cell proliferation and induce apoptosis (Zhang et al., 2009). Since cancer cells usually undergo active cell division (mitosis), a useful approach to finding anticancer drugs is to test whether a compound can selectively kill mitotic cells (Zhou et al. 2008). Therefore, cell cycle arrest is the special target for many anticancer drugs. Among them, taxanes, colchicines and vinca alkaloids are the well-known examples that induce the G2/M phase arrest leading to the subsequent apoptosis (Kim et al., 2011).
Apoptosis (programmed cell death) plays a crucial role in the homeostasis of organisms under both physiological and pathological conditions. Apoptosis is the most convenient manner of tumor cell elimination, as this type of cell death is a final state which does not cause any possible future danger (Flores et al., 2011). The two major pathways leading to apoptosis in cells includes: a) extrinsic pathway which involves the activation of the TNF/Fas death receptor family and the second one b) intrinsic pathway which involves mitochondria (Li et al., 2007).
Biochemically, apoptotic cells are characterized by the reduction of mitochondrial transmembrane potential, intracellular acidification, excessive production of reactive oxygen species (ROS), and externalization of phosphatidyl serine residues in membrane bilayers and selective proteolysis of cellular proteins and also further degradation of DNA into internucleosomal fragments. TRAIL( TNF related apoptosis inducing ligand) is a promising tool for cancer therapeutics due to its ability to selectively induce apoptosis in malignant tumor cells because it causes no toxicity against normal tissue. Agents that suppress the proliferation of malignant cells by inducing apoptosis may represent a useful mechanistic approach to both cancer chemoprevention and chemotherapy (Shafi et al., 2009). Therefore, induction of apoptosis in cancer cells is one of the useful strategies for the development of anticancer drugs.(HU et al., 2003).
Although a large number of synthetic drugs are being added to the world of modern pharmacopoeia, but still no system of medicine in the world which can solve all the health problems. Therefore the search for new therapeutic constituents from plants is genuine and urgent. Many plant-derived and natural products are being tested for their anti-cancer activities.
As a result of new approaches, the concept of achieving ideal health is changing, and focusses on the importance of a healthy lifestyle centered on diet and exercise. Diet as we all know plays a crucial role in the regulation of metabolic pathways genetically and epigenetically. By the help of modern genetics, and molecular biology, nutrition research will increasingly be able to apply new discoveries to develop designer functional foods by adding specific bioactive characteristics for preventing and reducing the risk of cancer development. Herbal medicines have been used since ancient times. They are usually a mixture of several compounds, which can affect cells. It is time to connect all these knowledge and experiences gathered over thousands of years in several civilizations to technology.
Another important problem of the treatment of cervical cancer is the resistance to chemotherapy and radiotherapy. In this review we observed that several polyphenols are able also to sensitize cervical cancer cells to conventional chemo- and radiation therapy. This combined approach could improve the efficiency of standard therapies and allow us to decrease the doses of chemotherapy drugs and irradiation leading to reduce the adverse side effects. We summarized in this article some of the polyphenolic compounds that have been studied until now for their possible anti-cancer therapeutic properties. It is crucial to continue these studies for searching therapeutic drugs from natural resource as well as for investigating their mechanism of action in cervical tumor cells.