Prostate cancer (PC) is one of the leading cause of cancer related deaths in men. PC progression and recurrence following initial treatments possesses mortality threat amongst these patients. Cell cycle re-entry of quiescent cancer cells has been suggested for cancer progression and recurrence. The slow progression of PC allows a window of opportunity for intervention through diet. An inverse association of flavonoids intake and PC development has been demonstrated in epidemiological studies. We hypothesized that citrus peel that is rich in various bioactive compounds including flavonoids may impede cell cycle re-entry by quiescent PC cells.
Actively proliferating prostate cancer cells (PC-3) were induced into quiescence by contact-inhibition. The cells were released from quiescence by diluting the cells to lower density in the presence of citrus peel extract.
Our study revealed that the experimental quiescent PC-3 progressed from G0/G1 to S phase following release from quiescence. Compared with the 20% reduction of G0/G1 cells upon cell cycle re-entry, only 3% reduction of G0/G1 cells was noted in the presence of citrus peel extract at 48 hours. In parallel, there was a significant decreased in DNA synthesis in PC-3 cells treated with the extract compared to the control as evaluated by EdU incorporation assay. The cell death was not observed in PC-3 cells when tested using Annexin V-FITC assay. Moreover, the compound responsible for inhibiting the cell cycle re-entry was isolated and identified using chromatographic method. Relevant analysis to validate the compound activity is underway.
This study suggests that citrus peel extract is able to inhibit the cell cycle re-entry of PC cells. The recovery and utilization of bioactive compounds from orange peel waste will open an avenue for developing affordable fortifying food products with potential to reduce the risk of cancer recurrence.
The University of Sydney
The University of Sydney and LangTech International Pty Ltd.
All authors have declared no conflicts of interest.