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Effects of various Flavonoids on apoptosis in HeLa, K562, HepG2 and MDCK cells

Numerous natural bioactive substances affect specific points in cell cycle or specific intracellular targets that change apoptosis, whether they encourage or block it. During the testing of these substances, it is important to determine whether the finding of apoptosis is normal variation, spontaneous disease or a change provoked by the tested substances. Flavonoids are known for their antitumor, anti-inflammatory, cardioprotective and immunomodulatory activities. It is believed that some of these biological effects are connected with their direct effects on the cell signaling pathways, while others are connected with their antioxidant properties, which are based on limiting the production of reactive oxygen compounds and/or their bonding. The aim of this study was to investigate the effects of myricetin, quercetin, kaempferol, apigenin and naringenin at concentrations of 0.1−10 μM on apoptosis and viability of HeLa, K562, HepG2, and MDCK cells. Antioxidant effect of flavonoids was investigated using ochratoxin A, which induces production of reactive oxygen species. Apoptotic cells were detected by the TUNEL method and quantified by flow cytometry (annexin V-FITC and PI). The mitotic and apoptotic indexes (hematoxylin and eosin) and levels of oxidized-reduced GSH-GSSG in the cells were determined, while the free radical scavenging ability (DPPH• assay) of flavonoids with different substitution patterns was tested. At concentrations of less than 1 μM flavonoids had no effects on cell death (apoptosis and necrosis) of the tested cells, while quercetin at 10 μM concentration induced apoptosis more intensively than other flavonoids. The myricetin showed the highest antiradical activity during the induced oxidative stress in MDCK cells.

Flavonoids; Apoptosis; Oxidative stress; HeLa; K562; HepG2; MDCK

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