The cytotoxicity of lingshuiol: a comparative study with amphidinol 2 on membrane permeabilizing activities.
The cytotoxicity of lingshuiol, a novel polyhydroxy compound with a linear carbon-chain isolated from the cultured marine dinoflagellate Amphidinium sp., and that of amphidinol 2 (AM2) was compared with hepatocytes. Both lingshuiol and AM2 were toxic to primary rat hepatocytes with IC(50) values of 0.21 and 6.4muM, respectively. Meanwhile, lingshuiol or AM2 caused a rapid mitochondrial swelling and leakage of Ca(2+), underlying the change in permeability of mitochondria. Cyclosporin A, a specific inhibitor of mitochondrial permeability transition (MPT), could not affect these effects, indicating that CsA-sensitive MPT was not involved in the permeabilizing effects of lingshuiol or AM2. Sytox green tests further demonstrated that lingshuiol had a much stronger permeabilizing activity than AM2. Taken together, these results disclosed that lingshuiol had potent membrane permeabilizing activities, which might account for its cytotoxic effect.
Qi
Xin-Ming
XM
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China.
Yu
Bo
B
Huang
Xiao-Chun
XC
Guo
Yue-Wei
YW
Zhai
Qing
Q
Jin
Ren
R
D000475:Alkenes / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004141:Dinoflagellida / Q000737:chemistry*; D022781:Hepatocytes / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D009930:Organic Chemicals; D011714:Pyrans / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000095722:Amphidinols
D000475:Alkenes; D002118:Calcium; D009930:Organic Chemicals; D011714:Pyrans; C402795:SYTOX Green; C523181:amphidinol 2; D000095722:Amphidinols; C523180:lingshuiol