Isorhamnetin (ISO), a naturally occurring plant
flavonoid, is widely used as a phytomedicine. The major treatment modality for
non-small-cell lung carcinoma (NSCLC) is
radiotherapy. However,
radiotherapy can induce radioresistance in
cancer cells, thereby resulting in a poor response rate. Our results demonstrated that pretreatment with ISO induced
radiosensitizing effect in A549 cells using colony formation, micronucleus, and γH2AX foci assays. In addition, ISO pretreatment significantly enhanced the radiation-induced incidence of apoptosis, the collapse of mitochondrial membrane potential, and the expressions of
proteins associated with cellular apoptosis and suppressed the upregulation of NF-κBp65 induced by irradiation in A549 cells. Interestingly, the expression of
interleukin-13 (IL-13), an anti-inflammatory
cytokine, was positively correlated with the ISO-mediated radiosensitization of A549 cells. The knockdown of
IL-13 expression by RNA interference decreased the
IL-13 level and thus reduced ISO-mediated radiosensitivity in cells. We also found that the IR-induced NF-κB signaling activation was inhibited by ISO pretreatment, and it was abrogated in
IL-13 silenced cells. We speculated that ISO may confer radiosensitivity on A549 cells via increasing the expression of
IL-13 and inhibiting the activation of NF-κB. To our knowledge, this is the first report demonstrating the effects of ISO treatment on the responsiveness of
lung cancer cells to irradiation through
IL-13 and the NF-κB signaling pathway. In summary, ISO is a naturally occurring radiosensitizer with a potential application in
adjuvant radiotherapy.