Open Access

Decrease of ABCB1 protein expression and increase of G1 phase arrest induced by oleanolic acid in human multidrug‑resistant cancer cells

  • Authors:
    • Didi Wang
    • Jincai Wang
    • Juan Zhang
    • Xin Yi
    • Jinhua Piao
    • Li Li
    • Jianjie Wang
    • Pengxia Zhang
    • Qiyang He
  • View Affiliations

  • Published online on: May 9, 2021     https://doi.org/10.3892/etm.2021.10167
  • Article Number: 735
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oleanolic acid (OA) is a natural compound that can be found in a number of edible and medicinal plants and confers diverse biological actions. However, the direct target of OA in human tumor cells remains poorly understood, preventing its application in clinical and health settings. A previous study revealed that overexpression of caveolin‑1 in human leukemia HL‑60 cells can increase its sensitivity to OA. The present study aimed to investigate the effects of OA on the doxorubicin‑resistant human breast cancer MCF‑7 cell line (MCF‑7/DOX), harringtonine‑resistant human leukemia HL‑60 cells (HL‑60/HAR) and their corresponding parental cell lines. Western blotting was performed to measure protein expression levels, whilst Cell Counting Kit‑8 (CCK‑8) assays, cell cycle analysis (by flow cytometry) and apoptosis assays (with Annexin V/PI staining) were used to assess drug sensitivity. CCK‑8 assay results suggested that MCF‑7/DOX cells, which overexpress the caveolin‑1 protein, have similar OA susceptibility to their parent line. In addition, sensitivity of MCF‑7/DOX cells to OA was not augmented by knocking down caveolin‑1 using RNA interference. HL‑60/HAR cells exhibited a four‑fold increased sensitivity to OA compared with that in their parental HL‑60 cells according to CCK‑8 assay. Both of the resistant cell lines exhibited higher numbers of cells at G1 phase arrest compared with those in their parent lines, as measured via flow cytometry. Treatment of both MCF‑7 cell lines with 100 µM OA for 48 h induced apoptosis, with increased effects observed in resistant cells. However, no PARP‑1 or caspase‑3 cleavage was observed, with some positive Annexin V staining found after HL‑60/HAR cells were treated with OA, suggesting that cell death occurred via non‑classical apoptosis or through other cell death pathways. It was found that OA was not a substrate of ATP‑binding cassette subfamily B member 1 (ABCB1) in drug‑resistant cells, as indicated by the accumulation of rhodamine 123 assessed using flow cytometry. However, protein expression of ABCB1 in both of the resistant cell lines was significantly decreased after treatment with OA in a concentration‑dependent manner. Collectively, these results suggest that OA could reduce ABCB1 protein expression and induce G1 phase arrest in multidrug‑resistant cancer cells. These findings highlight the potential of OA for cancer therapy.
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July-2021
Volume 22 Issue 1

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Spandidos Publications style
Wang D, Wang J, Zhang J, Yi X, Piao J, Li L, Wang J, Zhang P and He Q: Decrease of ABCB1 protein expression and increase of G1 phase arrest induced by oleanolic acid in human multidrug‑resistant cancer cells. Exp Ther Med 22: 735, 2021
APA
Wang, D., Wang, J., Zhang, J., Yi, X., Piao, J., Li, L. ... He, Q. (2021). Decrease of ABCB1 protein expression and increase of G1 phase arrest induced by oleanolic acid in human multidrug‑resistant cancer cells. Experimental and Therapeutic Medicine, 22, 735. https://doi.org/10.3892/etm.2021.10167
MLA
Wang, D., Wang, J., Zhang, J., Yi, X., Piao, J., Li, L., Wang, J., Zhang, P., He, Q."Decrease of ABCB1 protein expression and increase of G1 phase arrest induced by oleanolic acid in human multidrug‑resistant cancer cells". Experimental and Therapeutic Medicine 22.1 (2021): 735.
Chicago
Wang, D., Wang, J., Zhang, J., Yi, X., Piao, J., Li, L., Wang, J., Zhang, P., He, Q."Decrease of ABCB1 protein expression and increase of G1 phase arrest induced by oleanolic acid in human multidrug‑resistant cancer cells". Experimental and Therapeutic Medicine 22, no. 1 (2021): 735. https://doi.org/10.3892/etm.2021.10167