title: Potentiation of Acute Promyelocytic Leukemia Cell Differentiation and Prevention of Leukemia Development in Mice by Oleanolic Acid.
abstract: Although differentiation therapy with all-trans retinoic acid (ATRA) induces complete remission in most acute promyelocytic leukemia (APL) patients, it is associated with organ toxicity. The present study focused on investigating the effects of the natural compounds oleanolic acid (OA) and ursolic acid (UA) on proliferation and differentiation of human APL HL-60 cells in vitro and murine APL WEHI-3 cells in vivo. Results demonstrated that OA and UA significantly inhibited cellular proliferation of HL-60 in a concentration- and time-dependent manner. Non-cytotoxic concentration of OA exhibited a marked differentiation-inducing effect on HL-60 and enhanced ATRA-induced HL-60 differentiation. In contrast, UA showed only a moderate effect. Activation of MAPK/NF-κB signaling pathway was likely found to be involved in the mechanism. Moreover, OA increased survival duration of WEHI-3 transplanted BALB/c mice, and decreased leukemia cells infiltration in the liver and spleen. Thus, these results may provide new insight for developing alternative therapy in APL patients.
authors.affiliation: Department of Food Science, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C.
authors.forename: Reynetha D S
authors.initials: RD
authors.lastname: Rawendra
authors.affiliation: Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C.
authors.forename: Ping-Yuan
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C.
authors.forename: Ching-Dong
authors.initials: CD
authors.lastname: Chang
authors.affiliation: Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C. Research Center for Austronesian Medicine and Agriculture, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C. Research Center for Tropic Agriculture, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C.
authors.forename: Jue-Liang
authors.initials: JL
authors.lastname: Hsu
authors.affiliation: Department of Food Science, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C. Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C. Research Center for Austronesian Medicine and Agriculture, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C.
authors.forename: Tzou-Chi
authors.initials: TC
authors.lastname: Huang
authors.affiliation: Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C. Research Center for Austronesian Medicine and Agriculture, National Pingtung University of Science and Technology, Pingtung, Taiwan, R.O.C. wlshih@mail.npust.edu.tw.
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Shih
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000517:prevention & control*; D051379:Mice; D009828:Oleanolic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D014212:Tretinoin; D009828:Oleanolic Acid
keywords: Acute promyelocytic leukemia; WEHI-3; all-trans retinoic acid; differentiation; oleanolic acid