Pseudolaric acid B activates autophagy in MCF-7 human breast cancer cells to prevent cell death

Jinghua Yu, Chunhai Chen, Tianyang Xu, Minghui Yan, Bianbian Xue, Ying Wang, Chunyu Liu, Ting Zhong, Zengyan Wang, Xianying Meng, Donghua Hu, Xiaofang Yu

Research output: Contribution to journalArticle

Abstract

Pseudolaric acid B (PAB) has been demonstrated to exert antitumor effects in MCF-7 human breast cancer cells. The present study aimed to investigate the mechanism of resistance to PAB-induced cell death. Following incubation with 4 μM of PAB for 3 days, the majority of MCF-7 cells became senescent, while some retained the same morphology as control cells, as assessed using a senescence detection kit. Additionally, 36 h of treatment with 4 μM of PAB increased the positive staining of autophagy markers, as shown by monodansylcadaverine and acridine orange staining. Western blot analysis indicated that this treatment also increased expression of the autophagy-related proteins Beclin-1 and microtubule-associated protein 1 light chain 3. Furthermore, treatment with PAB and the autophagy inhibitor 3-methyl adenine significantly decreased the ratio of autophagy, as assessed by flow cytometric analysis of monodansylcadaverine staining density (P<0.001), and increased the ratio of cell death, as assessed by MTT analysis (P<0.001). This indicated that autophagy promotes cell survival as a resistance mechanism to PAB treatment. Additionally, the present study demonstrated that PAB treatment did not affect the mitochondrial membrane potential, which may be related to autophagy. Increased Bcl-2 expression may explain why PAB did not affect the mitochondrial membrane potential. A Bcl-2 binding test demonstrated that PAB treatment inhibits the binding of Bcl-2 and Beclin-1, which may free Beclin-1 to participate in autophagy. Therefore, the present study demonstrated that autophagy may be activated by PAB treatment in human breast cancer MCF-7 cells, contributing to resistance to cell death.

Original languageEnglish (US)
Pages (from-to)1731-1737
Number of pages7
JournalOncology Letters
Volume11
Issue number3
DOIs
StatePublished - Mar 2016

Keywords

  • Autophagy
  • MCF‑7 human breast cancer cells
  • Pseudolaric acid B

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Yu, J., Chen, C., Xu, T., Yan, M., Xue, B., Wang, Y., Liu, C., Zhong, T., Wang, Z., Meng, X., Hu, D., & Yu, X. (2016). Pseudolaric acid B activates autophagy in MCF-7 human breast cancer cells to prevent cell death. Oncology Letters, 11(3), 1731-1737. https://doi.org/10.3892/ol.2016.4103