6-O-Angeloylenolin induces apoptosis through a mitochondrial/caspase and NF-kappaB pathway in human leukemia HL60 cells

Abstract

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.