American Association for Cancer Research
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Supplementary Figure S4 from Hyperthermia Selectively Targets Human Papillomavirus in Cervical Tumors via p53-Dependent Apoptosis

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journal contribution
posted on 2023-03-30, 23:05 authored by Arlene L. Oei, Caspar M. van Leeuwen, Rosemarie ten Cate, Hans M. Rodermond, Marrije R. Buist, Lukas J.A. Stalpers, Johannes Crezee, H. Petra Kok, Jan Paul Medema, Nicolaas A.P. Franken

Induction of apoptosis determined using Nicoletti assay in HPV-positive and HPV-negative cells after radiation, hyperthermia and combined treatment in the presence or absence of P53-siRNA,cDDP, chloroquine or MG-132.



Human papillomavirus (HPV) is associated with cervical cancer, the third most common cancer in women. The high-risk HPV types 16 and 18 are found in over 70% of cervical cancers and produce the oncoprotein, early protein 6 (E6), which binds to p53 and mediates its ubiquitination and degradation. Targeting E6 has been shown to be a promising treatment option to eliminate HPV-positive tumor cells. In addition, combined hyperthermia with radiation is a very effective treatment strategy for cervical cancer. In this study, we examined the effect of hyperthermia on HPV-positive cells using cervical cancer cell lines infected with HPV 16 and 18, in vivo tumor models, and ex vivo–treated patient biopsies. Strikingly, we demonstrate that a clinically relevant hyperthermia temperature of 42°C for 1 hour resulted in E6 degradation, thereby preventing the formation of the E6–p53 complex and enabling p53-dependent apoptosis and G2-phase arrest. Moreover, hyperthermia combined with p53 depletion restored both the cell-cycle distribution and apoptosis to control levels. Collectively, our findings provide new insights into the treatment of HPV-positive cervical cancer and suggest that hyperthermia therapy could improve patient outcomes. Cancer Res; 75(23); 5120–9. ©2015 AACR.