PMID- 18097851 OWN - NLM STAT- MEDLINE DCOM- 20080327 LR - 20191210 IS - 0265-6736 (Print) IS - 0265-6736 (Linking) VI - 23 IP - 8 DP - 2007 Dec TI - Hyperthermia induces differentiation without apoptosis in permissive temperatures in human erythroleukaemia cells. PG - 645-55 AB - PURPOSE: The aim of the present study was to investigate whether induction of differentiation by hyperthermia is accompanied by apoptosis and necrosis to further evaluate the benefits of using hyperthermia as a differentiation inducing physical modality. MATERIALS AND METHOD: Differentiation was evaluated in K562 erythroleukaemia cells by measuring haemoglobin synthesis and flow cytometric measurement of glycophorin A expression. Apoptosis was measured by Annexin-V-FITC and Propidium Iodide (PI) double staining assay. Apoptosis and necrosis was also evaluated morphologically using staining with acridine orange/ethidium bromide (AO/EtBr) by fluorescence microscopy. Heat shock protein 70 (HSP70) level was measured by ELISA kit. RESULTS: Hyperthermia (43 degrees C) induced differentiation as judged by increased haemoglobin synthesis and glycophorin A expression. No sign of apoptosis or necrosis could be detected at this temperature. Cell viability did not change due to heat treatment, and cellular proliferation was reduced in a dose (heating time) dependent manner. At 45 degrees C, hyperthermia induced apoptosis and necrosis with minimal or no sign of differentiation. HSP70 level was significantly increased at 43 degrees C along with differentiation of leukaemic cells, while at 45 degrees C no significant effect on HSP70 production could be observed. CONCLUSIONS: The encouraging results obtained here indicate that by heat treatment at 43 degrees C, hyperthermia can be used alone or in combination with other modalities as a differentiation inducing agent without any detectable apoptotic activity. Positive correlation between HSP70 production and induction of differentiation and lack of apoptosis by hyperthermia confirm the possible role of HSP70 in the heat-induced differentiation and apoptosis in leukaemic cells. FAU - Sharif-Khatibi, Leila AU - Sharif-Khatibi L AD - Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. FAU - Kariminia, Amina AU - Kariminia A FAU - Khoei, Sameide AU - Khoei S FAU - Goliaei, Bahram AU - Goliaei B LA - eng PT - Evaluation Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Int J Hyperthermia JT - International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group JID - 8508395 RN - 0 (HSP70 Heat-Shock Proteins) SB - IM MH - Apoptosis/*physiology MH - Cell Differentiation/*physiology MH - Cell Proliferation MH - Cell Survival MH - Fever/metabolism/pathology MH - HSP70 Heat-Shock Proteins/metabolism MH - *Hot Temperature MH - Humans MH - K562 Cells MH - Leukemia, Erythroblastic, Acute/metabolism/*pathology MH - Temperature EDAT- 2007/12/22 09:00 MHDA- 2008/03/28 09:00 CRDT- 2007/12/22 09:00 PHST- 2007/12/22 09:00 [pubmed] PHST- 2008/03/28 09:00 [medline] PHST- 2007/12/22 09:00 [entrez] AID - 788717847 [pii] AID - 10.1080/02656730701769833 [doi] PST - ppublish SO - Int J Hyperthermia. 2007 Dec;23(8):645-55. doi: 10.1080/02656730701769833.