Specific regulation of HSPs in human tumor cell lines by flavonoids.
While the protective role HSPs (Heat Shock Proteins) has been recognized against physiological stress such as heat shock, heavy metals and glucose starvation, recent progress has revealed another aspect of HSPs in various diseases. HSP27 has been shown to be involved in the acquired resistance of tumor cells hyperthermic and chemotherapeutic treatment. In human breast tumors, overexpression of HSP27 is associated with a shorter disease-free survival period. HSP47 is thought to be a collagen specific molecular chaperone. The involvement of HSP47 in the progression of fibrosis has been reported. Aberrant expression of HSP could cause various autoimmune diseases. Manipulation of HSP expression, therefore, could be a therapeutic target to reduce HSP-derived detrimental cellular effects. Flavonoids are a widely distributed group of plant substances, universally present in vascular plants. Although the flavonoids have been known as natural plant products as long as the alkaloids, their pharmacological effects and potential medicinal uses have been little studied by comparison. Today, the picture has changed and the biological and pharmacological activities of plant flavonoids look promising. We investigated the effect of flavonoids on the expression of HSPs in human tumor cell lines. Flavonoids inhibited the expression of HSP27, HSP47, HSP60 and HSP72/73. The results suggested the pharmacological possibilities of flavonoids in diseases derived from abnormal expression of HSPs.
Morino
M
M
Kureha Chemical Industry Tokyo, Japan.
Tsuzuki
T
T
Ishikawa
Y
Y
Shirakami
T
T
Yoshimura
M
M
Kiyosuke
Y
Y
Matsunaga
K
K
Yoshikumi
C
C
Saijo
N
N
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms; D018834:Chaperonin 60 / Q000032:analysis / Q000235:genetics; D003110:Colonic Neoplasms; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D050884:HSP72 Heat-Shock Proteins; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms; D008175:Lung Neoplasms; D008297:Male; D009447:Neuroblastoma; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013274:Stomach Neoplasms; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D018834:Chaperonin 60; D005419:Flavonoids; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger