The Anti-Tumoral Role of Hesperidin and Aprepitant on Prostate Cancer cells through Redox Modifications

Abstract

Abstract Introduction: Prostate cancer is the second most frequent cancer in men. Aprepitant (AP) is a highly specific NK1R antagonist and its anti-cancer effects against different cancer cells including prostate cancer are shown previously. Also, the anti-cancer effect of Hesperidin has been shown in prostate cancer cells. While the anti-cancer effect of Hesperidin and AP on prostate cancer cells is well documented, their combined effect, as well as their mechanism of action are not fully understood. Therefore, the present study aimed to investigate the anti-cancer effects of Hesperidin and AP alone and in combination on prostate cancer cells. Method: PC3 and LNCaP cell lines were treated with Hesperidin and AP alone and in combination. The Resazurin test was used for assessing cell viability. The ROS (reactive oxygen Species) level, P53 and P21 gene expression, and Bcl-2 and Survivin gene expression were assessed in both cell lines. Also, a trypan blue assay was done for both cell lines. Results: The results of Resazurin showed that Hesperidin and AP significantly reduce the cell viability of PC3 and LNCaP cell lines. The ROS level significantly reduced after treating the PC3 and LNCaP cells with 10 µM AP with or without Hesperidin pretreatment. P53 and P21 gene expression significantly increased after treatment with 50 and 100 µM Hesperidin with or without 10 µM AP compared to the untreated group in the PC3 cell line. In addition, Bcl-2 and Survivin gene expression significantly decreased with 10 µM AP with or without Hesperidin pretreatment in the PC3 and LNCaP cell lines. Also, the results of the trypan blue assay showed the combination of Hesperidin with AP induced a high rate of apoptosis in LNCaP and PC3 cell lines. Conclusion: The current study showed the synergic anti-cancer effect of Hesperidin and Aprepitant on prostate cancer cells in both PC3 and LNCaP cell lines