Open Access

Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF‑κB signaling pathways in vitro

  • Authors:
    • Juan Luo
    • Yan‑Ling Hu
    • Hong Wang
  • View Affiliations

  • Published online on: August 18, 2017     https://doi.org/10.3892/etm.2017.4965
  • Pages: 3623-3631
  • Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer, which is the second leading cause of cancer‑associated mortality in women worldwide, develops from breast tissue. Chemotherapy is the most commonly used therapy to treat breast cancer. However, a number of natural plant‑derived products have been suggested as alternative therapies to treat different types of cancer, such as breast cancer. The aim of the present study was to determine the anti‑tumor effects of ursolic acid and its effect on apoptosis and inflammation in breast cancer cells. The anti‑cancer effects of ursolic acid were evaluated in vitro using flow cytometry, western blotting and reverse transcription‑quantitative polymerase chain reaction. The results suggest that ursolic acid inhibits the viability of breast cancer cells by inducing autophagy and apoptosis without inducing cell death. Cellular migration assays demonstrated that ursolic acid was able to suppress the invasive ability of breast cancer cells (P<0.05). In addition, the phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) pathway was downregulated following ursolic acid admini­stration (P<0.05), leading to an upregulation of glycogen synthase kinase activity (P<0.05) and downregulation of B‑cell lymphoma 2 (P<0.05), subsequently causing autophagy and apoptosis via cyclin‑D1 inhibition and caspase‑3 stimulation (P<0.05). Furthermore, the inflammatory response of breast cancer cells was assessed by measuring levels of nuclear factor (NF)‑κB. Ursolic acid was found to downregulate NF‑κB in breast cancer cells, thus inhibiting inflammation and preventing the progression of breast cancer (P<0.05). To the best of our knowledge, the present study is the first to assess the effect of ursolic acid on breast cancer cells through PI3K/AKT‑regulated GSK and caspase‑3 accompanied by NF‑κB signaling pathways. The results of the present study regarding the potential underlying molecular mechanisms of ursolic acid may be used to develop novel therapeutic strategies for breast cancer treatment.

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October-2017
Volume 14 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Luo J, Hu YL and Wang H: Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF‑κB signaling pathways in vitro. Exp Ther Med 14: 3623-3631, 2017.
APA
Luo, J., Hu, Y., & Wang, H. (2017). Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF‑κB signaling pathways in vitro. Experimental and Therapeutic Medicine, 14, 3623-3631. https://doi.org/10.3892/etm.2017.4965
MLA
Luo, J., Hu, Y., Wang, H."Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF‑κB signaling pathways in vitro". Experimental and Therapeutic Medicine 14.4 (2017): 3623-3631.
Chicago
Luo, J., Hu, Y., Wang, H."Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF‑κB signaling pathways in vitro". Experimental and Therapeutic Medicine 14, no. 4 (2017): 3623-3631. https://doi.org/10.3892/etm.2017.4965