Recombinant adenoviruses expressing apoptin suppress the growth of MCF‑7 breast cancer cells and affect cell autophagy

Oncol Rep. 2019 May;41(5):2818-2832. doi: 10.3892/or.2019.7077. Epub 2019 Mar 18.

Abstract

Autophagy and apoptosis both promote cell death; however, the relationship between them is subtle, and they mutually promote and antagonize each other. Apoptin can induce apoptosis of various tumor cells; however, tumor cell death is not only caused by apoptosis. Whether apoptin affects tumor cell autophagy is poorly understood. Therefore, the present study aimed to explore the potential mechanisms underlying the effects of apoptin using recombinant adenoviruses expressing apoptin. Reverse transcription‑quantitative polymerase chain reaction, immunoblotting, flow cytometry, fluorescence microscopy and proteomics analyses revealed that apoptin could induce autophagy in MCF‑7 breast cancer cells. The results also suggested that apoptin affected autophagy in a time‑ and dose‑dependent manner. During the early stage of apoptin stimulation (6 and 12 h), the expression levels of autophagy pathway‑associated proteins, including Beclin‑1, microtubule‑associated protein 1A/1B‑light chain 3, autophagy‑related 4B cysteine peptidase and autophagy‑related 5, were significantly increased, suggesting that apoptin promoted the upregulation of autophagy in MCF‑7 cells. Conversely, after 12 h of apoptin stimulation, the expression levels of apoptosis‑associated proteins were decreased, thus suggesting that apoptosis may be inhibited. Therefore, it was hypothesized that apoptin may enhance autophagy and inhibit apoptosis in MCF‑7 cells at the early stage. In conclusion, apoptin‑induced cell death may involve both autophagy and apoptosis. The induction of autophagy may inhibit apoptosis, whereas apoptosis may inhibit autophagy; however, occasionally both pathways operate at the same time and involve apoptin. This apoptin‑associated selection between tumor cell survival and death may provide a potential therapeutic strategy for breast cancer.

MeSH terms

  • Adenoviridae / genetics
  • Apoptosis / drug effects
  • Autophagy / genetics*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Capsid Proteins / genetics*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Female
  • Genetic Vectors / genetics
  • Humans
  • MCF-7 Cells
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses / genetics

Substances

  • Capsid Proteins
  • VP3 protein, Chicken anemia virus