Proapoptotic effect of a dietary supplement: water soluble chitosan activates caspase-8 and modulating death receptor expression.
The effect of water-soluble chitosan, a natural polymer used as a dietary supplement, on human bladder-tumor cells was investigated. Apoptotic morphological change was demonstrated by nuclear staining. Chitosan-treated cells showed elevation of caspase-8-like activity, but no significant elevation of caspase-9-like activity, which suggest that proapoptotic effect of chitosan is attributable to death receptor activation and not to activation of the mitochondria-cytochrome c pathway. Chitosan increased expression of TNF-R1, but decreased Fas expression. Use of monoclonal antibodies to inhibit death-receptor signal transduction did not attenuate the proapoptotic activity of chitosan. Examination of death-ligands revealed that TNFalpha mRNA expression was markedly increased by chitosan treatment while FasL mRNA was not affected. Although the direct interaction of chitosan with death receptors remains unidentified, the results suggest that its proapoptotic effect might be related to interaction with TNFalpha or TNF-R1.
Takimoto
Hiroyuki
H
Department of Clinical Pharmacy, Kobe Pharmaceutical University, Japan.
Hasegawa
Masumi
M
Yagi
Keiko
K
Nakamura
Tsutomu
T
Sakaeda
Toshiyuki
T
Hirai
Midori
M
D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D048271:Chitosan; D019587:Dietary Supplements; D004789:Enzyme Activation / Q000187:drug effects; D053222:Fas Ligand Protein; D006801:Humans; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D002686:Chitin; D048271:Chitosan; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases