Natural Phenolic Antioxidants, Tumor Suppressor And Its Mechanism

Recent years, the progressions from the field of free radical biology have been figuringout the role of reaction oxygen species (ROS) in maintaining and promoting the malignantphenotypes of tumor, and uncovering the modulation role of ROS on cell signal pathway.On the other hand, the effects of natural phenolic antioxidants on anti-ROS, cancer inhibitionand regulation of signal pathway have been respectively proved by many reports. However,the relationship between the anti-ROS property of phenolic antioxidants and inhibiting cancerproliferation is needed to be proved. Described in this Part are the works on trying to provethis relationship by revealing and comparing the cancer inhibition ways and mechanisms ofselected natural phenolic antioxidants Isoverbascoside (Isov) and low concentration curcumin.To compare the cancer inhibition ways, Isov and curcumin were designed as Isov,curcumin and Isov plus curcumin three groups. The human stomach cancer MGC 80-3 andhuman hepatocarcinoma SMMC-7721 cell lines were engaged as the research model. Effectsof three drug groups on cell proliferation, morphology, activities of differentiation markerenzymes, colony formation and growth of nude mouse xenografe tumor were measured by themethods from cell and molecular biology, biochemistry and free radical biology. Forelucidating the cancer inhibition mechanisms, the effects of thee phenolic antioxidants groupson cell cycles and related gene expression, intracellular redox were measuredThe results revealed that:â‘ Inducing cell differentiation is the cancer inhibition way of Isov, while curcumin can onlycause reversible inhibition cell proliferation, however, curcumin can enhance the inducingdifferentiation effect of Isov.â‘¡The reason of Isov caused G₀/G₁ arresting is association to enhancing p53, p21 and pi6genes expression. Curcumin only causes G₂/M arresting.â‘¢The mechanism of differentiation induced by Isov is association to its ability of enhancingp53 expression, arresting G₀/G₁ and down-regulating NFκB, cjun/AP-1 and c-myc genesexpression. Lacking up-regulation of p53 expression and G₀/G₁ arresting may be the majorreason of reversible inhibition caused by curcumin.â‘£By down-regulating intracellular oxidative stress and then inhibiting cell proliferationsignal pathway may be a causation of Isov and curcumin inhibiting cell growth.⑤The anti-ROS property of natural phenolic antioxidant is relation to its cancer inhibitionfunction. However, the cancer inhibition way is major decided by their chemical structure.Taken together, the results in this Part have initially proved that the anti-ROS property ispartially relation to the cancer inhibition of phenolic antioxidants. The anti-cancer way ismajor association to the core molecular structure of phenolic antioxidants. These results maybe useful for elucidation of mechanism of different cancer inhibition ways by natural phenolicantioxidants, and helpful for understanding the mechanism of inducing differentiation. .Recent years, photodynamic therapy (PDT) has been proved as applicable method forhead and neck cancer therapy. The curative effect of PDT is largely decided by thephotosensitizer hemotopropyrin derivative (HPD), an only photosensitizer admited for clinicalapplication. The quality of HPD made in our country has been proved unsuitable forachievement good curative effect. The import HPD. though possession high curative effect, isvery costliness. Although no reports about inducing solid cancer cell apoptosis,.photosensitized curcumin and photosensitized riboflavin have been reported having cytotoxityon some cancer cells. For the propose of developing applicable and low side effect new typephotosensitizer for enhancing photodynamic therapy of HPD, the inducing apoptosis effectsand mechanisms of photosensitized curcumin and photosensitized riboflavin were initiallystudied using human stomach cancer cell line MGC 80-3 as researching model. The results showed that: Curcumin, photosensitized curcumin and photosensitized riboflavin all have the effect ofinducing cell apoptosis, and photosensitized curcumin may possess more efficiency ofinducing apoptosis than curcumin if on same concentration. The G2/M arresting induced by three drugs suggest an association between G2/M arrestingand cell apoptosis. Up-regulating c-myc, p53 and bax, plus down-regulating bcl-2 gene expression may presentthe molecular mechanism of inducing apoptosis by photosensitized curcumin andphotosensitized riboflavin. Down-regulating bcl-2 expression suggest an association betweenbcl-2 declining and apoptosis induced by curcumin. Photosensitized curcumin and photosensitized riboflavin may share the same mechanismthrough producing ROS by photochemical reaction and then inducing cell apoptosis. However,no evidence prove that curcumin can produce large amount ROS intracellular. In conclusion, the results described in this Port suggested a potential application ofphotosensitized curcumin and photosensitized riboflavin as new type photosensitizer in tumorphotodynamic therapy.