Resveratrol inhibits viability and induces apoptosis in the small‑cell lung cancer H446 cell line via the PI3K/Akt/c‑Myc pathway

Oncol Rep. 2020 Nov;44(5):1821-1830. doi: 10.3892/or.2020.7747. Epub 2020 Sep 1.

Abstract

There have been no major breakthroughs in the treatment of small‑cell lung cancer (SCLC) in recent decades. It is thus essential to explore new or adjuvant treatment options for SCLC. Resveratrol (Res) is a natural antioxidant revealed to influence the entire process of cancer development. Accordingly, the present study used the SCLC cell line H446 to explore the antitumor mechanism of Res. Cells were treated with 40 µg/ml Res with or without pretreatment with the antioxidant N‑acetyl‑L‑cysteine (NAC). H446 cell viability and apoptosis were assessed with MTT and flow cytometry, and the expression of cytochrome c and the PI3K/Akt/c‑Myc pathway and the nuclear translocation of apoptosis inducing factor (AIF) were assessed by western blotting. In addition, the changes in ROS content and mitochondrial membrane potential were determined. The results revealed that Res inhibited H446 cell viability and induced apoptosis, increased cytochrome c expression, inhibited the expression of PI3K/Akt/c‑Myc signaling pathway components, and promoted the translocation of AIF from the cytoplasm to the nucleus in H446 cells. However, NAC pretreatment reversed these changes to various extents. The results of the present study indicated that Res may inhibit the viability and promote the apoptosis of human SCLC H446 cells through the PI3K/Akt/c‑Myc pathway and that oxidative stress and mitochondrial membrane potential depolarization may be involved in the aforementioned processes.

Keywords: resveratrol; small-cell lung cancer; PI3K/Akt/c-Myc pathways.

MeSH terms

  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Apoptosis Inducing Factor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Reactive Oxygen Species / metabolism
  • Resveratrol / pharmacology*
  • Signal Transduction / drug effects
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / metabolism
  • Small Cell Lung Carcinoma / pathology

Substances

  • Antioxidants
  • Apoptosis Inducing Factor
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Reactive Oxygen Species
  • Cytochromes c
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • Resveratrol