Lei Ning1, Weichong Zhao, Hua Gao, Yanlin Wu. 1. Department of Clinical Laboratory, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, 250013, P. R. China.
Abstract
PURPOSE: Hesperidin, a plant-based molecule, has been shown to exhibit anticancer effects against the human prostate cancer cells. However, its mechanism of action is still unclear. This study was undertaken to investigate the mechanism underlying the anticancer effects of hesperidin against prostate cancer cells. METHODS: The CCK-8 kit-based proliferation analysis was performed to find out the effect of hesperidin administration on prostate cancer cell growth, in vitro. Apoptosis of cancer cells was studied with dual Annexin V-FITC/propidium iodide (PI) staining combined with flow cytometry. The latter was also used for the analysis of cancer cell mitotic cell cycle. The intracellular levels of reactive oxygen species (ROS) were determined with ROS-detection kit. Fluorescent probing was used for determination of mitochondrial membrane potential (MMP) of prostate cancer cells. The migration and invasion of cancer cells was studied using transwell assay. RESULTS: The in vitro treatment of prostate cancer cells led to significant decrease of cell growth and viability in a dose-dependent manner. The decline in the growth of cancer cells was shown to be resulting from initiation of cell cycle arrest and necrosis-like apoptotic cell death. The latter was shown to be triggered by intracellular accumulation of ROS molecules and reduction of MMP. Moreover, the hesperidin administration significantly reduced the cancer cell migration and invasion. CONCLUSION: Hesperidin was shown to selectively inhibit the growth of prostate cancer cells through apoptosis triggered by ROS generation. The results support its potential to act as lead molecule in anticancer drug design.
PURPOSE:Hesperidin, a plant-based molecule, has been shown to exhibit anticancer effects against the humanprostate cancer cells. However, its mechanism of action is still unclear. This study was undertaken to investigate the mechanism underlying the anticancer effects of hesperidin against prostate cancer cells. METHODS: The CCK-8 kit-based proliferation analysis was performed to find out the effect of hesperidin administration on prostate cancer cell growth, in vitro. Apoptosis of cancer cells was studied with dual Annexin V-FITC/propidium iodide (PI) staining combined with flow cytometry. The latter was also used for the analysis of cancer cell mitotic cell cycle. The intracellular levels of reactive oxygen species (ROS) were determined with ROS-detection kit. Fluorescent probing was used for determination of mitochondrial membrane potential (MMP) of prostate cancer cells. The migration and invasion of cancer cells was studied using transwell assay. RESULTS: The in vitro treatment of prostate cancer cells led to significant decrease of cell growth and viability in a dose-dependent manner. The decline in the growth of cancer cells was shown to be resulting from initiation of cell cycle arrest and necrosis-like apoptotic cell death. The latter was shown to be triggered by intracellular accumulation of ROS molecules and reduction of MMP. Moreover, the hesperidin administration significantly reduced the cancer cell migration and invasion. CONCLUSION:Hesperidin was shown to selectively inhibit the growth of prostate cancer cells through apoptosis triggered by ROS generation. The results support its potential to act as lead molecule in anticancer drug design.