Active Hexose-correlated Compound Down-regulates Heat Shock Factor 1, a Transcription Factor for HSP27, in Gemcitabine-resistant Human Pancreatic Cancer Cells.
BACKGROUND
Active hexose-correlated compound (AHCC) is an extract of a basidiomycete mushroom that enhances the therapeutic effects and reduces the side-effects of chemotherapy. Our previous studies demonstrated that heat-shock protein 27 (HSP27) was involved in gemcitabine-resistance of pancreatic cancer cells and it was down-regulated by AHCC-treatment. However, how AHCC down-regulated HSP27 is unknown. In the present study, we focused on two transcription factors reported to induce HSP27, heat shock factor 1 (HSF1) and high-mobility group box 1 (HMGB1) and investigated the effect of AHCC on their expression.


METHODS
KLM1-R cells were treated with AHCC and the protein expression of HSF1 and HMGB1 were analyzed by western blotting.


RESULTS
The protein expression of HSF1 in KLM1-R was down-regulated by AHCC treatment. On the other hand, the protein expression of HMGB1 was not reduced in KLM1-R cells after AHCC treatment.


CONCLUSIONS
The possibility that AHCC down-regulated HSP27 through down-regulation of the HSF1, was herein shown.
Departments of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Masayuki
M
Tokunaga
Departments of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Byron
B
Baron
Departments of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Takao
T
Kitagawa
Departments of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Kazuhiro
K
Tokuda
Departments of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan climates@yamaguchi-u.ac.jp.
Yasuhiro
Y
Kuramitsu
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011134:Polysaccharides / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C000619706:HSF1 protein, human; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011134:Polysaccharides; D014157:Transcription Factors; D003841:Deoxycytidine; C499366:Active Hexose Correlated Compound; D000093542:Gemcitabine
AHCC; HMGB1; HSF1; HSP27; gemcitabine; pancreatic cancer