N-(beta-Elemene-13-yl)tryptophan methyl ester induces apoptosis in human leukemia cells and synergizes with arsenic trioxide through a hydrogen peroxide dependent pathway.
Beta-elemene is an active component of herb medicine Curcuma Wenyujin and N-(beta-elemene-13-yl)tryptophan methyl ester (ETME) was synthesized for increasing its antitumor activity. ETME induced apoptosis in human leukemia HL-60 and NB4 cells at concentrations less than 40 microM. The apoptosis induction ability of ETME was associated with the production of hydrogen peroxide (H(2)O(2)), the decrease of mitochondrial membrane potential, and the activation of caspase-3 that was blocked by catalase. ETME in combination with arsenic trioxide (As(2)O(3)), an agent used to treat acute promyelocytic leukemia, synergistically induced apoptosis in both cell lines by enhanced production of H(2)O(2). These data suggest that ETME induces apoptosis and synergizes with As(2)O(3) in leukemia cells through a H(2)O(2)-dependent pathway.
Yu
Zhiying
Z
Shenyang Pharmaceutical University, Shenyang 110015, China.
Wang
Rui
R
Xu
Liying
L
Dong
Jinhua
J
Jing
Yongkui
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D053148:Caspase 3 / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D001152:Arsenicals; C532393:N-(beta-elemene-13-yl)tryptophan methyl ester; D010087:Oxides; D012717:Sesquiterpenes; C445979:beta-elemene; D014364:Tryptophan; D006861:Hydrogen Peroxide; D002374:Catalase; D053148:Caspase 3; D000077237:Arsenic Trioxide