Abstract

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.

Highlights

  • Isorhamnetin (ISO), a flavonoid isolated from traditional Chinese medicine (Hippophae L.), has been known to have antioxidative and anti-inflammatory effects and immunomodulatory properties (Echeverry et al, 2004; Seo et al, 2014)

  • Our results demonstrated that ISO could sensitize A549 cells to radiation via inhibition of Nuclear Factor-κB (NF-κB) activation mediated by upregulating the level of antiinflammatory interleukin-13 (IL-13)

  • To investigate whether ISO treatment could enhance the radiosensitivity of cells, two non-small-cell lung carcinoma (NSCLC) cell lines were treated with 20 μM ISO for 24 h and irradiated with different doses of radiation

Read more

Summary

Introduction

Isorhamnetin (ISO), a flavonoid isolated from traditional Chinese medicine (Hippophae L.), has been known to have antioxidative and anti-inflammatory effects and immunomodulatory properties (Echeverry et al, 2004; Seo et al, 2014). Through disrupting mitochondrial membrane potential (MMP), ISO promoted the release and activation of cytochrome c and caspases 3 and 9 and induced A549 cells apoptosis (Li et al, 2015). NSCLC has been historically considered as a radioresistant malignancy; conventional chemotherapy or radiotherapy is usually poor in cure rate for cancer patients. In order to identify promising radiosensitivity agents, a large number of natural products with anti-inflammatory, antioxidant, and antitumor activations have been considered (Li et al, 2017; Sun et al, 2017). ISO, a natural product, has these features and is safe, available, and of better efficacy. Can it be potentially served as a radiosensitizer for cancer treatment?

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call