Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway

PLoS One. 2017 Apr 17;12(4):e0175977. doi: 10.1371/journal.pone.0175977. eCollection 2017.


Radiotherapy is a powerful tool in the treatment of cancer that has the advantage of preserving normal tissues. However, tumor radioresistance currently remains a major impediment to effective RT. Thus, exploring effective radiation sensitizers is urgently needed. In this study, we have shown that diosmetin, the aglycone of the lavonoid glycoside from olive leaves, citrus fruits and some medicinal herbs, has a promising effect on radiotherapy sensitization. In our results, DIO could induce G1 phase arrest and thus enhance the radiosensitivity of radioresistant A549/IR lung cancer cells. Furthermore, DIO also restrains the IR-induced DNA damage repair by inhibiting the activated Akt signaling pathway. The combination of Akt inhibition (DIO, LY294002 or MK-2206) and radiation potently blocked A549/IR cancer cell proliferation. In summary, these observations suggest that the natural compound DIO could act as a potential drug for the treatment of radioresistant lung cancer cells.

MeSH terms

  • A549 Cells
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chromones / pharmacology
  • DNA Repair / drug effects
  • Flavonoids / pharmacology*
  • G1 Phase / drug effects
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Humans
  • Lung Neoplasms / drug therapy*
  • Morpholines / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Radiation Tolerance / drug effects*
  • Radiation-Sensitizing Agents / pharmacology*
  • Signal Transduction / drug effects*


  • Chromones
  • Flavonoids
  • Heterocyclic Compounds, 3-Ring
  • MK 2206
  • Morpholines
  • Radiation-Sensitizing Agents
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-akt
  • diosmetin

Grants and funding

This work is supported by the National Natural Science Foundation of China (No. 81572946), Changsha Science and Technology Project (No. k1508024-31), and Clinical and Rehabilitation Research Foundation of Xiangya hospital - Beidaweiming.