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Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA

  • Authors:
    • Lanzhen Huang
    • Ang Li
    • Guanzhen Liao
    • Feicheng Yang
    • Jing Yang
    • Xu Chen
    • Xiaoshan Jiang

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  • Published online on: May 29, 2017     https://doi.org/10.3892/ol.2017.6273
  • Pages: 1080-1088
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Abstract

Triple-negative breast cancer (TNBC; estrogen receptor-negative, progesterone receptor‑negative and Her‑2‑negative) is often accompanied by a higher frequency of p53 gene mutations. Therefore, TNBC is challenging to treat due to a lack of biological targets and a poor sensitivity to conventional therapies. Curcumol is a monomer composition isolated from the ethanol extracts of Curcuma wenyujin, a Chinese medicinal herb traditionally used as a cancer remedy. Previous studies have revealed that curcumol is able to block proliferation in various human tumor cell lines. However, the underlying mechanisms have yet to be elucidated. The present study aimed to investigate the anticancer effects of curcumol in the human p53 mutant TNBC MDA‑MB‑231 cell line and its underlying mechanisms. Cell viability and growth were determined by MTT and a mice xenograft model assay, respectively. Cell cycle distribution was examined by flow cytometry. Apoptosis was evaluated by apoptotic morphology analysis with DAPI staining and flow cytometric analysis following Annexin V/propi­dium iodide staining. The protein expression in cells was eva­luated by immunoblotting. Treatment of MDA‑MB‑231 cells with curcumol resulted in a significant inhibition of cell proliferation in vitro [half maximal inhibitory concentration (IC50)=240.7±85.0 µg/ml for 48 h and IC50=100.2±13.5 µg/ml for 72 h]. Curcumol treatment also resulted in the suppression of xenograft growth in vivo (100 or 200 µg/kg for 21 days), as well as G1 phase arrest and an apoptotic response, which were accompanied by the upregulation of p73 expression and the activation of the expression of p53 upregulated modulator of apoptosis (PUMA) and Bcl‑2 antagonistic killer (Bak). No cleavage of poly (ADP‑ribose) polymerase was detected. To the best of our knowledge, the present data demonstrate for the first time that curcumol inhibits the growth of MDA‑MB‑231 cells and triggers p53‑independent apoptosis, which may be media­ted by the p73‑PUMA/Bak signaling pathway. Curcumol may, therefore, be a potential compound for use in the development of novel TNBC therapeutics.
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July-2017
Volume 14 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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  • Impact Factor: 2.5
  • Ranked Oncology
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  • CiteScore: 5.7
  • CiteScore Rank: Q2: #139/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.574
  • SCImago Journal Rank (SJR): 0.644
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Spandidos Publications style
Huang L, Li A, Liao G, Yang F, Yang J, Chen X and Jiang X: Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA. Oncol Lett 14: 1080-1088, 2017.
APA
Huang, L., Li, A., Liao, G., Yang, F., Yang, J., Chen, X., & Jiang, X. (2017). Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA. Oncology Letters, 14, 1080-1088. https://doi.org/10.3892/ol.2017.6273
MLA
Huang, L., Li, A., Liao, G., Yang, F., Yang, J., Chen, X., Jiang, X."Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA". Oncology Letters 14.1 (2017): 1080-1088.
Chicago
Huang, L., Li, A., Liao, G., Yang, F., Yang, J., Chen, X., Jiang, X."Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA". Oncology Letters 14, no. 1 (2017): 1080-1088. https://doi.org/10.3892/ol.2017.6273