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Oleanolic acid derivatives induce apoptosis in human leukemia K562 cell involved in inhibition of both Akt1 translocation and pAkt1 expression

Cytotechnology volume 67, pages 821–829 (2015)Cite this article

Abstract

Oleanolic acid (OA) derivatives exhibit numerous pleiotropic effects in many cancers. The present study aimed to investigate the molecular mechanisms of 5′-amino-oleana-2,12-dieno[3,2-d]pyrimidin-28-oic acid (compound 4) and oleana-2,12-dieno[2,3-d]isoxazol-28-oic acid (compound 5) inducing apoptosis in human leukemia K562 cell. We investigated the effects of the compounds on K562 cell growth, apoptosis and cell cycle. The compounds showed strong inhibitory effects on K562 cell viability in a dose-dependent manner determined by the 3-(4,5-dimethylthiazoyl)-2,5-diphenyltetrazolium bromide assay and significantly increased chromatin condensation and apoptotic bodies in K562 cells. Flow cytometry assay suggested that the compounds induced inhibition of K562 cell proliferation associated with G1 phase arrest. In addition, the compounds inhibited Akt1 recruiting to membrane in CHO cells which express Akt1-EGFP constitutively and down-regulated the expression of pAkt1 in K562 cell. These results suggested that the compounds can efficiently inhibit proliferation and induce apoptosis perhaps involved in inactivation of Akt1. The OA derivatives may be potential chemotherapeutic agents for the treatment of human cancer.

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Abbreviations

OA:

Oleanolic acid

DMSO:

Dimethyl sulphoxide

FBS:

Fetal bovine serum

PI:

Propidium Iodide

MTT:

3-(4,5-dimethylthiazoyl)-2,5-diphenyltetrazolium bromide

PMSF:

Phenylmethanesulfonyl fluoride

PVDF:

Polyvinylidene fluoride

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Acknowledgments

This work is supported in part by International Cooperation Project (5-16), Zhejiang Provincial NSF (Y4110320), NSFC (Nos. 20972086, 21172130), and Opening Foundation of Zhejiang Biomedicine Engineering Key Discipline.

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Affiliations

  1. College of Life Science, Zhejiang Sci-Tech University, Xiasha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, China

    Shuhua Pan, Tingting Zheng, Xinyuan Liu & Chuanlian Xu

  2. Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Tsinghua University, Haidian District, Beijing, 100084, China

    Jun Hu & Yong Ju

  3. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China

    Xinyuan Liu

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  1. Shuhua Pan
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  2. Jun Hu
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  3. Tingting Zheng
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  4. Xinyuan Liu
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  5. Yong Ju
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  6. Chuanlian Xu
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Correspondence to Chuanlian Xu.

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Pan, S., Hu, J., Zheng, T. et al. Oleanolic acid derivatives induce apoptosis in human leukemia K562 cell involved in inhibition of both Akt1 translocation and pAkt1 expression. Cytotechnology 67, 821–829 (2015). https://doi.org/10.1007/s10616-014-9722-3

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Keywords

  • Oleanolic acid derivatives
  • Leukemia
  • Chronic myeloid
  • Apoptotic body
  • G1 phase
  • Akt1-EGFP