Effects of HPV Status on Responsiveness to Ionizing Radiation vs Photodynamic Therapy in Head and Neck Cancer Cell lines

• Published in: Photochemistry and photobiology 2020-05, Vol.96 (3), p.652-657
• Main Authors: Kessel, David, Cho, Won Jin, Rakowski, Joseph, Kim, Harold E., Kim, Hyeong‐Reh C.
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Biotechnology; Cancer; Cell death; Cell Line, Tumor; Head & neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - radiotherapy; Head and Neck Neoplasms - virology; Human papillomavirus; Humans; Ionizing radiation; Mortality; Papillomaviridae - isolation & purification; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - pharmacology; Radiation, Ionizing; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - radiotherapy; Squamous Cell Carcinoma of Head and Neck - virology; Tumor cell lines; Viruses
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/php.13150

Efficacy of ionizing radiation (I/R) was compared with phototoxic effects of photodynamic therapy (PDT) in vitro using two cell lines derived from patients with head and neck squamous cell carcinoma (HNSCC). A cell line derived from a donor with a human papilloma virus (HPV) infection was more responsive to I/R but significantly less responsive to PDT than a cell line derived from an HPV‐free patient. Cell death after I/R in the HPV(+) cell line was associated with increased DEVDase activity, a hallmark of apoptosis. The HPV(−) line was considerably less responsive to I/R, with DEVDase activity greatly reduced, suggesting an impaired apoptotic program. In contrast, the HPV(−) cells were readily killed by PDT when the ER was among the targets for photodamage. While DEVDase activity was enhanced, the death pathway appears to involve paraptosis until the degree of photodamage reached the LD99 range. These data suggest that PDT‐induced paraptosis can be a death pathway for cells with an impaired apoptotic program. This image demonstrates the ability of photodynamic therapy (PDT) directed at ER/mitochondria to eradicate a head & neck cancer cell line (WSU12) from a patient with a human papilloma virus infection. These cells were relatively unresponsive to ionizing radiation, typical of HPV (+) tumors. In contrast, cells from an HPV (−) patient (UP154) were responsive to ionizing radiation but not to PDT.