Molecular-weight-dependent toxic effects of chitosans on the human keratinocyte cell line HaCaT.
The cationic polysaccharide chitosan possesses bioactive properties such as antimicrobial activity, antitumor effects, hemostatic assets and positive effects on wound healing. The influence of polycations like chitosan on human cells has been reported to depend on their molecular weight. However, the mechanism of cytotoxicity caused by polycations is not yet fully understood. In the study presented, the influence of two chitosans with a similar degree of deacetylation but different molecular weight, chitosan 1130 (120 kDa) and chitosan oligosaccharide (5 kDa), on the human keratinocyte cell line HaCaT was analyzed. The results obtained indicate that chitosans exhibit a molecular-weight-dependent negative effect on HaCaT cell viability and proliferation in vitro. The chitosans tested also stimulated the release of inflammatory cytokines by HaCaT cells depending on incubation time and concentration. Chitosan 1130 and chitosan oligosaccharide induced apoptotic cell death which was mediated by activation of the effector caspases 3/7. At least for chitosan 1130, the involvement of both, extrinsic and intrinsic signal pathways, was shown by activation of caspases 8 and 9.
Wiegand
C
C
Department of Dermatology, University Medical Center, Jena, Germany. C.Wiegand@med.uni-jena.de
Winter
D
D
Hipler
U-C
UC
D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D009844:Oligosaccharides / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D009844:Oligosaccharides; D048271:Chitosan; D020169:Caspases