Proton versus photon radiation–induced cell death in head and neck cancer cells
Li Wang MD, PhD
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorShichao Han MD
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Department of Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
Search for more papers by this authorJinming Zhu MD
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Department of Radiation Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
Search for more papers by this authorXiaochun Wang PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorYuting Li PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorZeming Wang BS
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorEric Lin MS
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorXiaofang Wang MD, PhD
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorDavid P. Molkentine BS
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorPierre Blanchard MD
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorYining Yang MS
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorRuiping Zhang MS
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorNarayan Sahoo PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorMichael Gillin PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorXiaorong Ronald Zhu PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorXiaodong Zhang PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorJeffrey N. Myers MD, PhD
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorCorresponding Author
Steven J. Frank MD
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Correspondence
Steven J. Frank, Department of Radiation Oncology, Unit 1422, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030.
Email: [email protected]
Search for more papers by this authorLi Wang MD, PhD
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorShichao Han MD
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Department of Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
Search for more papers by this authorJinming Zhu MD
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Department of Radiation Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
Search for more papers by this authorXiaochun Wang PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorYuting Li PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorZeming Wang BS
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorEric Lin MS
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorXiaofang Wang MD, PhD
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorDavid P. Molkentine BS
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorPierre Blanchard MD
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorYining Yang MS
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorRuiping Zhang MS
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorNarayan Sahoo PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorMichael Gillin PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorXiaorong Ronald Zhu PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorXiaodong Zhang PhD
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorJeffrey N. Myers MD, PhD
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
Search for more papers by this authorCorresponding Author
Steven J. Frank MD
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Correspondence
Steven J. Frank, Department of Radiation Oncology, Unit 1422, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030.
Email: [email protected]
Search for more papers by this authorAbstract
Background
Photon (X-ray) radiotherapy (XRT) kills cells via DNA damage, however, how proton radiotherapy (PRT) causes cell death in head and neck squamous cell carcinoma (HNSCC) is unclear. We investigated mechanisms of HNSCC cell death after XRT versus PRT.
Methods
We assessed type of death in 2 human papillomavirus (HPV)-positive and two HPV-negative cell lines: necrosis and apoptosis (Annexin-V fluorescein isothiocyanate [FITC]); senescence (β-galactosidase); and mitotic catastrophe (γ-tubulin and diamidino-phenylindole [DAPI]).
Results
The XRT-induced or PRT-induced cellular senescence and mitotic catastrophe in all cell lines studied suggested that PRT caused cell death to a greater extent than XRT. After PRT, mitotic catastrophe peaked in HPV-negative and HPV-positive cells at 48 and 72 hours, respectively. No obvious differences were noted in the extent of cell necrosis or apoptosis after XRT versus PRT.
Conclusion
Under the conditions and in the cell lines reported here, mitotic catastrophe and senescence were the major types of cell death induced by XRT and PRT, and PRT may be more effective.
CONFLICT OF INTEREST
Steven J. Frank is an advisory board member and consultant for Varian Medical Systems.
Supporting Information
| Filename | Description |
|---|---|
| hed25357-sup-0001-FigureS1A.TIFapplication/tif, 220.2 KB | Fig. S1. Necrosis and apoptosis in four head and neck squamous cell carcinoma cell lines after photon (XRT) or proton (PRT) irradiation. Two HPV-negative cell lines (SqCC/Y1 and HN5) and two HPV+ cell lines (UPCI-SCC-154 and UMSCC-47) were exposed to a single 4-Gy dose of XRT or PRT. At 4 hours, 24 hours, or 48 hours after irradiation, cells were subjected to terminal deoxy-nucleotidyltransferase (TdT) dUTP nick-end labeling (TUNEL) assay and incubated with FITC-conjugated Annexin V and propidium iodide and analyzed by BD Accuri C6. Percentages of necrotic or apoptotic cells were quantified with FlowJo V10 software. Panel A-D: Representative flow cytometry plots for each cell line. |
| hed25357-sup-0001-FigureS1B.TIFapplication/tif, 208.5 KB | Fig. S1B. |
| hed25357-sup-0001-FigureS1C.TIFapplication/tif, 183 KB | Fig. S1C. |
| hed25357-sup-0001-FigureS1D.TIFapplication/tif, 217.3 KB | Fig. S1D. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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