Fisetin, a phytopolyphenol, targets apoptotic and necroptotic cell death in HepG2 cells

AbstractFisetin (3,7,3 ′,4′‐tetrahydroxyflavone), a bioactive dietary flavonoid, intrigued scientists for its anticancer potential against various cancer types. We investigated the fisetin‐induced inhibition of growth and survival of human hepatocellular carcinoma. Fisetin decreased cell viability and proliferatio n of HepG2 cells as revealed from MTT and clonogenicity assays. Cell cycle arrest in the G2/M phase was observed. Annexin V/propidium iodide (PI) staining followed by flow cytometry revealed that fisetin induced both apoptosis and necroptosis in HepG2 cells. Apoptotic cells were significantly increa sed on fisetin treatment as observed in morphological evaluations and 4′,6‐diamidino‐2‐phenylindole and Acridine orange staining. Flow cytometry, fluorescence imaging, and 2′, 7′‐dichlorofluorescein diacetate analyses showed an increase in reactive oxygen species (ROS) generation on fi setin treatment. Pretreatment withN‐acetyl cysteine inhibited ROS production and also rescued mitochondrial membrane potential in HepG2 cells. The underlying mechanisms of apoptosis and necroptosis were determined by analysis of their respective signaling molecules using qRT‐PCR and Western blotting. Fisetin showed a marked incre ase in the expression of TNFα and IKκB with a decrease in NF‐κB, pNF‐κB and pIKκB expression. Fisetin reduced the expression of Bcl2, and elevated levels of Bax, caspase‐3, and PARP and thus induced apoptosis in HepG2 cells. zV...
Source: BioFactors - Category: Biochemistry Authors: Tags: RESEARCH COMMUNICATION Source Type: research