6-O-Angeloylenolin induces apoptosis through a mitochondrial/caspase and NF-kappaB pathway in human leukemia HL60 cells.
6-O-Angeloylenolin, a sesquiterpene lactone from Centipeda minima, has been known to have anti-tumor activity against human colorectum, liver, stomach, lung, and skin tumor cells. However, its molecular mechanism is still obscure and insufficient in in vivo tests. In this study, we demonstrated that 6-O-angeloylenolin could induce apoptosis in human leukemia HL60 cells through stimulating the generation of reactive oxygen species, decreasing mitochondrial trans-membrane potential (DeltaPsim) and activating caspase-3/7. We also found that 6-O-angeloylenolin could inhibit nuclear translocation of NF-kappaB and modulate the expression of Bcl-2 gene family. These results indicated that 6-O-angeloylenolin induces apoptosis by inhibition of NF-kappaB activation, modulation of Bcl-2 gene family expression and destruction of mitochondrial function. Furthermore, we confirmed that 6-O-angeloylenolin could obviously inhibit the solid cancer growth in Lewis lung cancer xenograft models.
Changlong
Li
L
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
Hezhen
Wu
W
Yongping
Huang
H
Yanfang
Yang
Y
Yanwen
Liu
L
Jianwen
Liu
L
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019659:Asteraceae / Q000737:chemistry; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053179:Caspase 7 / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
C531937:6-O-angeloylenolin; D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D053148:Caspase 3; D053179:Caspase 7