Ursodeoxycholic acid prevents apoptosis of mouse sensory neurons induced by cisplatin by reducing P53 accumulation.
Ursodeoxycholic acid (UDCA), a component of bile acid, which is abundant in the gall bladder of bears, has been used in clinical medicine for cholestatic liver diseases. Recently, it was demonstrated that UDCA and its derivative tauroursodeoxycholic acid block apoptotic cell death in both hepatic and non-hepatic cells. Cisplatin, an effective anti-cancer drug, is known to cause sensory neuropathy in patients receiving the drug. In the present study, whether UDCA is effective in blocking cisplatin-induced cell death in mouse hybrid sensory neurons was conducted. N18D3 mouse hybrid sensory neurons exposed to cisplatin were found to undergo apoptotic cell death. Preincubation with UDCA completely blocked cisplatin-induced apoptotic cell death in the sensory neurons, and cisplatin-induced p53 accumulation was suppressed by UDCA treatment. These results indicate that UDCA has a neuroprotective effect on the cisplatin-induced neuronal cell death of sensory neurons via the downregulation of the p53 signaling pathway.
Institute for Regenerative Medicine, Gachon University Gil Medical Center, 534-2 Yeonsu-dong, Inchon 406-799, Republic of Korea.
In H
IH
Park
Mi K
MK
Kim
Seung U
SU
Kim
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D019610:Cytoprotection; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018696:Neuroprotective Agents; D016159:Tumor Suppressor Protein p53; D014580:Ursodeoxycholic Acid; D002945:Cisplatin