Oleanolic acid inhibits proliferation and induces apoptosis in NB4 cells by targeting PML/RARα

Li,Hongmei; He,Ning; Li,Xueyan; Zhou,Li; Zhao,Mingyu; Jiang,Hairui; Zhang,Xiaojie

doi:10.3892/ol.2013.1497

Oleanolic acid inhibits proliferation and induces apoptosis in NB4 cells by targeting PML/RARα

Authors:
- Hongmei Li
- Ning He
- Xueyan Li
- Li Zhou
- Mingyu Zhao
- Hairui Jiang
- Xiaojie Zhang
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Affiliations: Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Institute of Polygenic Disease, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Central Laboratory, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Vascular Surgery, Third Affiliated Hospital, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Cardiology, Second Affiliated Hospital, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Pathology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China
Published online on: July 29, 2013 https://doi.org/10.3892/ol.2013.1497
Pages: 885-890

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Abstract

Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid contained in a variety of plant species, exhibits broad biological properties, including anticancer effects. Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia. APL has a unique and specific chromosomal aberration, t(15;17), which results in the formation of a fusion gene and protein PML/RARα, which is not only necessary for the diagnosis of APL, but is also critical for APL pathogenesis. In the present study, the cytotoxic effect of OA on NB4 cells was investigated. Cell viability was assessed via the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. The expression levels of bax and bcl‑2 mRNA were determined by quantitative PCR. Apoptosis was analyzed using DNA fragment analysis and cell cycle distributions were analyzed by flow cytometry. The activity of caspase‑3 and caspase‑9 was determined by colorimetric assays. The expression of the PML/RARα fusion protein was analyzed by western blotting. The MTT assay showed that OA inhibited the proliferation of the NB4 cells. The expression levels of pro‑apoptotic bax mRNA were increased and the levels of anti‑apoptotic bcl‑2 mRNA were decreased following the treatment of the NB4 cells with OA at 80 µmol/l. Treatment of the NB4 cells with OA at 80 µmol/l induced apoptosis and G1 phase arrest, while caspase‑9 and caspase‑3 activity was significantly increased. Furthermore, the expression of the PML/RARα fusion protein was decreased. Together, these data suggest that OA exerts a cytotoxic effect that inhibits proliferation and induces apoptosis in NB4 cells by targeting PML/RARα, making it a potent therapeutic agent against leukemia.

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