title: Oleanolic acid induces apoptosis in human leukemia cells through caspase activation and poly(ADP-ribose) polymerase cleavage.
abstract: It has been shown that Fructus Ligustri Lucidi (FLL), a promising traditional Chinese medicine, can inhibit the growth of tumors. However, the effective component and molecular mechanism of FLL act to inhibit tumor proliferation are unclear. In this study, we demonstrated that oleanolic acid (OA), a principal chemical component of FLL, inhibited the proliferation of human leukemia HL60 cells in culture. MTT assay showed that treatment of HL60 cells with FLL crude extracts or OA dramatically blocked the growth of target tumor cell in a time- and dose-dependent manner. Morphological changes of the nuclei and DNA fragmentation showed that apoptotic cell death occurred in the HL60 cells after treating with FLL extracts (20 mg/ml) or OA (3.65 x 10(-2) mg/ml). Furthermore, flow cytometry assay showed that treatment of HL60 cells with FLL or OA caused an increased accumulation of G(1) and sub-G(1) subpopulations. Western blot analysis showed that caspase-9 and caspase-3 were activated, accompanied by the cleavage of poly(ADP-ribose) polymerase (PARP) in the target cells during FLL- or OA-induced apoptosis. These results suggest that OA acts as the effective component of FLL by exerting its cytotoxicity towards target tumor cells through activation of caspases and cleavage of PARP.
authors.affiliation: Department of Histology and Embryology, Guangdong Medical College, Zhanjiang 524023, China.
authors.forename: Pengxia
authors.initials: P
authors.lastname: Zhang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Juhua
authors.initials: J
authors.lastname: Ni
authors.forename: Yuming
authors.initials: Y
authors.lastname: Kang
authors.forename: Shuqiu
authors.initials: S
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D004789:Enzyme Activation / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D006868:Hydrolysis; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D009828:Oleanolic Acid / Q000502:physiology* / Q000627:therapeutic use; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009828:Oleanolic Acid; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases