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: Reynetha D S Rawendra, Ping-Yuan Lin, Ching-Dong Chang, Jue-Liang Hsu, Tzou-Chi Huang, Wen-Ling Shih
• Journal: Anticancer research (Anticancer Res) Vol. 35 Issue 12 Pg. 6583-90 (Dec 2015) ISSN: 1791-7530 [Electronic] Greece
• PMID: 26637873 (Publication Type: Journal Article)
• Copyright: Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Tretinoin
• Oleanolic Acid

Topics

• Animals
• Cell Differentiation
• Cell Proliferation
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy, prevention & control)
• Mice
• Oleanolic Acid (pharmacology, therapeutic use)
• Tretinoin (metabolism)