Li Wang1, Shichao Han1,2, Jinming Zhu1,3, Xiaochun Wang4, Yuting Li4, Zeming Wang4, Eric Lin1, Xiaofang Wang1, David P Molkentine1, Pierre Blanchard5,6, Yining Yang4, Ruiping Zhang4, Narayan Sahoo4, Michael Gillin4, Xiaorong Ronald Zhu4, Xiaodong Zhang4, Jeffrey N Myers7, Steven J Frank5. 1. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 2. Department of Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. 3. Department of Radiation Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China. 4. Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 5. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 6. Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France. 7. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Abstract
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.
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.
Authors: Nicolette Taku; Li Wang; Adam S Garden; David I Rosenthal; G Brandon Gunn; William H Morrison; C David Fuller; Jack Phan; Jay P Reddy; Amy C Moreno; Michael T Spiotto; Gregory Chronowski; Shalin J Shah; Lauren L Mayo; Neil D Gross; Renata Ferrarotto; X Ronald Zhu; Xiaodong Zhang; Steven J Frank Journal: Curr Treat Options Oncol Date: 2021-06-04
Authors: Alexander D Sherry; Dario Pasalic; G Brandon Gunn; C David Fuller; Jack Phan; David I Rosenthal; William H Morrison; Erich M Sturgis; Neil D Gross; Maura L Gillison; Renata Ferrarotto; Adel K El-Naggar; Adam S Garden; Steven J Frank Journal: Int J Part Ther Date: 2021-06-25
Authors: Alexander N Hanania; Xiaodong Zhang; G Brandon Gunn; David I Rosenthal; Adam S Garden; C David Fuller; Jack Phan; Jay P Reddy; Amy Moreno; Gregory Chronowski; Shalin Shah; Noveen Ausat; Ehab Hanna; Renata Ferrarotto; Steven J Frank Journal: Int J Part Ther Date: 2021-06-25