Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells

British Journal of Cancer
J V HettingaH H Kampinga

Abstract

In this study, the mechanism(s) by which heat increases cis-diamminedichloroplatinum (cisplatin, cDDP) sensitivity in cDDP-sensitive and -resistant cell lines of murine as well as human origin were investigated. Heating cells at 43 degrees C during cDDP exposure was found to increase drug accumulation significantly in the cDDP-resistant cell lines but had little effect on drug accumulation in the cDDP-sensitive cell lines. DNA adduct formation, however, was significantly increased in all cell lines studied. Furthermore, ongoing formation of platinum (Pt)-DNA adducts after the end of cDDP treatment was enhanced and/or adduct removal was decreased in heated cells, resulting in relatively more DNA damage remaining at 24 h after the end of cDDP exposure. Correlation plots with survival revealed weak correlations with cellular Pt accumulation (r2 = 0.59) and initial Pt-DNA adduct formation (r2 = 0.64). Strong correlations, however, were found with Pt-DNA adducts at 6 h (r2 = 0.97) and 24 h (r2 = 0.89) after the incubation with the drug. In conclusion, the mechanism by which heat sensitizes cells for cDDP action seems to be the sum of multiple factors, which comprise heat effects on accumulation, adduct formation and adduct processin...Continue Reading

Citations

Aug 12, 2009·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Valeria MilaniRolf Issels
Apr 12, 2016·Indian Journal of Surgical Oncology·Aditi Bhatt, Olivier Glehen
Nov 14, 1997·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·J V HettingaH H Kampinga
Jun 15, 2007·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·J W J BergsC van Bree
Oct 24, 2007·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Erito MochikiHiroyuki Kuwano
Jan 10, 2012·World Journal of Gastrointestinal Oncology·Antonio MacrìEdoardo Saladino
Jun 5, 2015·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Mayra L SottileSilvina B Nadin
Jul 28, 2020·The Journal of Obstetrics and Gynaecology Research·Hideaki TsuyoshiYoshio Yoshida
Jan 7, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sae Hee KoDouglas S Tyler
Sep 27, 2018·Gynecologic Oncology·Oliver ZivanovicRoisin E O'Cearbhaill
Jun 19, 2021·Annals of Surgical Oncology·Aditi BhattOlivier Glehen
May 14, 2004·Neoplasia : an International Journal for Oncology Research·Ardith W El-Kareh, Timothy W Secomb
Nov 30, 2010·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·M DeracoS Kusamura

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