Abstract B22: Selective responses of HepG2 cancer cells and primary hepatocytes to growth regulatory effects of Fe (II) and herbal tea flavonoids
Authors: Samodien Sedicka , Kock Maryna de , Swanevelder Sonja , Joubert Elizabeth , Gelderblom Wentzel 
Published: December 2017

Abstract
The role of flavonoids as chemopreventive agents is complex due to flavonoid-cell interactions affecting oxidative stress parameters known to play a key role in cell growth and survival. The current study investigated differential anti-proliferative and pro-apoptotic effects and modulation of oxidative status by unfermented (Rg) and polyphenol-enriched (PERg) rooibos (Aspalathus linearis) extracts, while the interaction with Fe (II) in liver cancer (HepG2) cells and primary rat hepatocytes were critically assessed. In contrast to the rooibos extracts, Fe (II) increased cell proliferation in HepG2 cells while in primary hepatocytes both viability and proliferation was decreased. Fe (II) countered the reduction in cell viability and inhibition of proliferation by either Rg or the PERg extracts in HepG2 cells, implying a protective effect. Similar treatments did not significantly alter the growth parameters in primary hepatocytes. Pre-exposure of HepG2 cells to Fe (II) tended to also counteract the reduction in cell viability induced by Rg and PERg while no effect was noticed in primary rat hepatocytes. The PERg extract was more prominent in affecting apoptosis in HepG2 cells, while the opposite was noticed in primary hepatocytes where Rg was more effective. In both cases, Fe (II) counteracted the induction of apoptosis, which was associated with an increase in cell viability. Pre-exposure to iron provide little protective effects, although the induction of apoptosis was markedly reduced, suggesting that a memory effect existed following Fe (II) exposure in both cell culture systems. Thus, Fe (II) decreased the susceptibility of the cells to the effects of the rooibos extracts presumably due to the chelating properties by counteracting the pro-oxidant effects of the rooibos flavonoids.
The modulation of cell viability and proliferation by rooibos flavonoids are related to their redox-sensitivity. Both extracts significantly increased glutathione (GSH) levels in HepG2 cells, while only the highest Rg extract concentration resulted in an increase in primary rat hepatocytes. This response is indicative of an antioxidant cellular response presumably by adapting to an oxidative insult effect by the rooibos extracts. Co-exposure with Fe (II) in HepG2 cells counteracted the effects of the rooibos extracts by normalizing the GSH content similar to that of the control level. Pre-exposing cells to Fe (II) showed little memory effect on the reduction of GSH content as the levels was significantly increased above that affected by the rooibos extracts in HepG2 cells suggesting an increased insult on the redox status. In primary hepatocytes a similar effect was noticed although to a far lesser extent. The activity of glutathione peroxidase (GPx) was significantly decreased by the rooibos extracts, while Fe (II) tended to counteract the reduction during the combined and pre-exposure models in both cell culture systems. The reduction in the GPx activity was more prominent in the primary hepatocytes. Understanding the underlying flavonoid/Fe (II) interactions and the modulation of cellular oxidative status and cell growth parameters will provide valuable information to reduce the risk of exposure to polyphenol-enriched neutraceuticals and food supplements in humans.
Citation Format: Sedicka Samodien, Maryna de Kock, Sonja Swanevelder, Elizabeth Joubert, Wentzel Gelderblom. Selective responses of HepG2 cancer cells and primary hepatocytes to growth regulatory effects of Fe (II) and herbal tea flavonoids [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B22.