Radiotherapy, a frequent mode of cancer treatment, is often restricted by dose-related toxicity and development of therapeutic resistance. Fisetin is a natural flavonoid found in various fruits and vegetables and has shown anticancer and radiosensitizing effect in lung and prostate cancer. Considering its anticancer activity, we studied the effect and mechanism of Fisetin-induced inhibition of growth and survival of human HNC cells in combination with radiation treatment. We found that Fisetin enhances X-ray-induced inhibition (up to 83%, P &lt; 0.001) of colony formation in HNC cells followed by G2-M arrest. MitoSOX analyses showed an increase in mitochondrial Reactive Oxygen Species (ROS) generation and mitochondrial membrane depolarization in Fisetin-treated HNC cells. Combination of Fisetin and radiation increased the apoptosis up to 53%. Further more, tagging HNC cells with mito-GFP and mito-RFP showed elevation in the frequency of mictochondial exchange in radiation treated cells. Flow cytometry analysis for EMT markers showed that cells having dual mitochondrial population also have high expression of vimentin and reduced expression of E-cadherin in comparison to single mitochondrial population. This dual mitochondrial population is more resistant and less responsive toward radiation treatment. However, Fisetin pre-treated cells upon radiation treatment reduced the rate of mitochondrial exchange in HNC cells. Immunoblotting analysis suggested that Fisetin treatment for HNC cells inhibit the expression of pDRP1-ser316 and total DRP1 and induces the expression of MFN1&2 and p53. These results suggest that Fisetin plays an important role in inhibiting the mitochondrial exchange between cancer cells and sensitizes them for radiation treatment. Detailes of in vitro and in vivo data of our investigations will be presented.

Fisetin sensitize the head and neck cancer (HNC) cells to radiation treatment via mitochondrial exchange inhibition

255th National Meeting (2018)

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