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Acacetin, a bioflavanoid, contains anti-inflammatory and anti-cancer activities as shown in different experimental models. However, its anticancer potential and mechanism of action against colorectal cancer cells is largely unknown. Here, we have investigated the efficacy of acacetin using two colorectal adenocarcinoma SW480 and HCT-116 cell lines. Cell survival was examined by Trypan-blue exclusion and MTT assays, cell cycle analysis by FACS, apoptosis was assessed using Annexin V FITC assay and nuclear condensation by Hoechst staining, ROS level by DCFDA and Mitosox, and protein expression level by Western blotting. Acacetin reduced the cell survival and proliferation of both types of cells, and induced S- and G2-M phase arrest and also reduced the levels of β-catenin and its downstream target c-myc. Further, acacetin induced apoptosis as examined by Annexin-V FITC and nuclear condensation. It increased intracellular ROS production, especially mitochondrial ROS. Acacetin increased mitochondrial membrane potential depolarization and Bax:Bcl-2 ratio. Although significant changes in caspases -8 and -9 and PARP level was not observed, acacetin could induce the truncation and subsequent translocation of activated AIF from mitochondria to cytosol, which could further induce chromosomal breakage leading to apoptosis. In conclusion, Acacetin induces mitochondrial ROS-mediated cell death in a caspase-independent manner in SW480 and HCT-116 colon carcinoma cells by inducing apoptosis inducing factor (AIF), which may potentiate its anticancer and chemotherapeutic prospects against colorectal carcinoma.

The cellular systems of living organisms are orchestrated with crucial events of constant production and removal of reactive oxygen species under physiological conditions. This plays an important biological role of maintenance of redox homeostasis and provides protection against oxidative stress-induced chronic and degenerative diseases. This chapter includes a detailed discussion on oxidative stress-induced inflammatory diseases such as asthma, cardiovascular diseases, diabetes, cancer and neurodegenerative diseases. Also, the modern approaches to studying oxidative stress-induced pathologies and key molecules that could act as therapeutic targets have been highlighted. The identification of oxidative stress as a common denominator to these diseases and the respective molecular targets that trigger these pathologies can potentially lead to novel approaches in disease prevention and health maintenance, especially via the use of nutraceuticals and/or phytochemicals. The paradoxical role of these nutraceuticals narrates the difficulties in using them clinically. Therefore, enhanced understanding of biochemical activities of nutraceuticals will enable them as better therapeutic options in oxidative stress-induced diseases.