Eriodictyol exerts potent anticancer activity against A549 human lung cancer cell line by inducing mitochondrial-mediated apoptosis, G2/M cell cycle arrest and inhibition of m-TOR/PI3K/Akt signalling pathway.

Abstract

IntroductionEriodictyol is an important flavonoid and is commonly present across the plant kingdom. Flavonoids have been reported to show incredible pharmacological potential. However, the anticancer activity of the important flavonoid eriodictyol has not been well reported. In the present study we determined its anticancer potential against the human lung cancer cell line A549.Material and methodsThe initial cytotoxicity induced by eriodictyol was measured by MTT assay. Flow cytometry was used to study the effects of eriodictyol on apoptosis, cell cycle phase distribution and mitochondrial membrane potential loss. The comet assay was used to measure DNA damage induced by eriodictyol in cancer cells while the western blot assay indicated effects of the compound on Bax/Blc-2 and PI3K/AKT/m-TOR proteins.ResultsThe results showed that eriodictyol has an IC50 value of 50 μM against human lung cancer cells as compared to the IC50 of 95 µM against non-cancerous FR2 cells. The molecule exerted its anticancer activity through induction of apoptosis by regulating the Bcl-2/Bax signalling pathway. It caused cell cycle arrest of human lung cancer A549 cells at G2/M phase. Eriodictyol was also found to cause a reduction of the mitochondrial membrane potential in a dose-dependent manner. Additionally, eriodictyol effectively inhibited the mTOR/PI3K/Akt signalling pathway in a dose-dependent manner.ConclusionsBased on the above findings, we conclude that eriodictyol exerts its anticancer activity through induction of mitochondrial apoptosis and G2/M cell cycle arrest and inhibition of the TOR/PI3K/Akt cascade, indicating that it may have potential as a lead compound in the treatment of lung cancer, provided further in depth studies are done.