Actinodaphnine induces apoptosis through increased nitric oxide, reactive oxygen species and down-regulation of NF-kappaB signaling in human hepatoma Mahlavu cells.
Actinodaphnine, extracted from Cinnamomum insularimontanum (Lauraceae), possesses cytotoxicity in some cancers, but the mechanism by which actinodaphnine induces apoptosis in human hepatoma cells remains poorly understood. In this study, we investigated the mechanisms of apoptosis induced by actinodaphnine in human hepatoma Mahlavu cells. Treatment with actinodaphnine dose-dependently induced apoptosis in Mahlavu cells that correlated with increased intracellular nitric oxide (NO) and reactive oxygen species (ROS), disruptive mitochondrial transmembrane potential (DeltaPsi(m)), and activation of caspase 3/7. Our data also demonstrated that actinodaphnine down-regulated activity of nuclear factor kappaB (NF-kappaB). The apoptotic response to actinodaphnine was markedly decreased in Mahlavu cells pretreated with dexsamethasone, a NO inhibitor, N-acetylcysteine (NAC), an antioxidant, and Boc-Asp(OMe)-fmk, a broad caspases inhibitor. These results suggested that actinodaphnine-induced apoptosis is initially mediated through the NO and/or ROS increase and caspases-dependent pathway. In conclusion, our results indicate that an increase of ROS and/or NO is the initial essential event that results in the decrease of DeltaPsi(m) and the activation of caspases that commits the cells to the apoptotic pathway in actinodaphnine-treated hepatoma Mahlavu cells.
Hsieh
Tian-Jye
TJ
Basic Medical Science Education Center, Fooyin University, Taiwan, ROC.
Liu
Tsan-Zon
TZ
Lu
Fung-Jou
FJ
Hsieh
Pei-Ying
PY
Chen
Ching-Hsein
CH
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D004249:DNA Damage; D004148:Dioxolanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D020287:In Situ Nick-End Labeling; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004148:Dioxolanes; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C060992:actinodaphine; D020169:Caspases