The cytotoxicity induced by brucine from the seed of Strychnos nux-vomica proceeds via apoptosis and is mediated by cyclooxygenase 2 and caspase 3 in SMMC 7221 cells.
To study the cytotoxicity of four alkaloids: brucine, strychnine, brucine N-oxide and isostrychnine from nux vomica on SMMC 7721 cells and their possible mechanisms, MET assay was used to examine the growth inhibitory effects of these alkaloids. Brucine revealed the strongest growth inhibitory effect on SMMC-7721 cells. Furthermore, as directly observed under an inverted microscope, fluorescent microscope and transmission electronic microscope, brucine caused SMMC-7721 cell shrinkage, membrane blobbing, formation of apoptotic body as well as nucleus condensation, all of which are typical characteristics of apoptotic programmed cell death. In addition, brucine dose-dependently caused SMMC-7721 cells apoptosis via formation of subdipolid DNA and phosphatidylserine externalization, as evidenced by flow cytometry analysis. The brucine-induced apoptosis was partially attributed to the activation of caspase 3 as well as cyclooxygenase 2 inhibition, since neither caspase 3 specific inhibitor, z-DEVD-fmk nor was exogenous addition of prostaglandin E(2) able to completely abrogate the brucine-induced SMMC 7721 cell apoptosis. In sum, this paper indicate that the major alkaloids present in the seed of Strychnos nux-vomica are effective against SMMC-7721 cells proliferation, among which brucine proceeds SMMC-7721 cells death via apoptosis, probably through the participation of caspase 3 and cyclooxygenase 2.
Yin
Wu
W
State Key Lab of Pharmaceutical Biotechnology, Nanjing University, 210093, China.
Deng
Xu-Kun
XK
Yin
Fang-Zhou
FZ
Zhang
Xiao-Chun
XC
Cai
Bao-Chang
BC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology; D053148:Caspase 3 / Q000096:biosynthesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology; D012639:Seeds / Q000737:chemistry; D013331:Strychnine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D031461:Strychnos nux-vomica / Q000737:chemistry
D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; C083067:brucine N-oxide; C083806:brucine; D051546:Cyclooxygenase 2; D053148:Caspase 3; D013331:Strychnine