Homoharringtonine induces heat protection and facilitates dissociation of heat shock transcription factor and heat shock element complex.
We investigated the effects of combined treatment with homoharringtonine (HHT) and hyperthermia on cytotoxicity and transcriptional regulation of heat shock genes in human colon carcinoma (HT-29) cells. The drug (100 ng/ml) which inhibited protein synthesis by 93% protected cells from killing at 43 degrees C. For example, treatment with HHT 2 hr before and during heating produced a 9-fold increase in survival from 3.7 x 10(-2) to 3.2 x 10(-1) after 10 hr at 43 degrees C. Little or no protection was observed if the drug was added only during heating. Interestingly, adding the drug (100 ng/ml) 2 hr before and during heat facilitated the dissociation of heat shock transcription factor-heat shock element (HSF-HSE) complex during continuous heating at 43 degrees C. These findings related to the literature suggest that the free pool of HSC70 is increased by inhibiting protein synthesis. An increase in the level of free HSC70 may more effectively protect or repair thermolabile targets and consequently affect regulation of heat shock response.
Lee
Y J
YJ
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073.
Hou
Z Z
ZZ
Erdos
G
G
Cho
J M
JM
Corry
P M
PM
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006248:Harringtonines / Q000494:pharmacology*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D000077863:Homoharringtonine; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006248:Harringtonines; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; D000077863:Homoharringtonine