Radiosensitization of non-small cell lung cancer by kaempferol.
The aim of the present study was to determine whether kaempferol has a radiosensitization potential for lung cancer in vitro and in vivo. The in vitro radio-sensitization activity of kaempferol was elucidated in A-549 lung cancer cells by using an MTT (3-(4 5-dimethylthiazol-2-yl)-25-diphenyl-tetrazolium bromide) assay, cell cycle analysis and clonogenic assay. The in vivo activity was evaluated in the BALB/c nude mouse xenograft model of A-549 cells by hematoxylin and eosin staining and immunohistochemistry, and the tumor volume was recorded. Protein levels of the apoptotic pathway were detected by western blot analysis. Treatment with kaempferol inhibited the growth of A-549 cells through activation of apoptotic pathway. However, the same doses did not affect HFL1 normal lung cell growth. Kaempferol induced G2/M cell cycle arrest and the enhancement of radiation-induced death and clonogenic survival inhibition. The in vivo data showed that kaempferol increased tumor cell apoptosis and killing of radiation. In conclusion, the findings demonstrated that kaempferol increased tumor cell killing by radiation in vitro and in vivo through inhibition of the AKT/PI3K and ERK pathways and activation of the mitochondria apoptosis pathway. The results of the present study provided solid evidence that kaempferol is a safe and potential radiosensitizer.
Institute of Biomedical Engineering, National Taiwan University, Taipei 10051, Taiwan, R.O.C.
Wei-Ting
WT
Kuo
Graduate Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan, R.O.C.
Yuan-Chung
YC
Tsai
School of Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
His-Chin
HC
Wu
Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan, R.O.C.
Yung-Jen
YJ
Ho
Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan, R.O.C.
Yueh-Sheng
YS
Chen
Viator Catholic High School, Taichung 40402, Taiwan, R.O.C.
Chen-Han
CH
Yao
Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan, R.O.C.
Chun-Hsu
CH
Yao
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000532:radiotherapy*; D020935:MAP Kinase Signaling System; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D044949:Kaempferols; D011838:Radiation-Sensitizing Agents; C006552:kaempferol; D019869:Phosphatidylinositol 3-Kinases