Betaine suppresses cell proliferation by increasing oxidative stress-mediated apoptosis and inflammation in DU-145 human prostate cancer cell line

Cell Stress Chaperones. 2019 Sep;24(5):871-881. doi: 10.1007/s12192-019-01022-x. Epub 2019 Jul 31.

Abstract

Prostate cancer is the main cause of cancer-related mortality in men around the world and an important health problem. DU-145 human prostate cancer cells provide an opportunity to investigate prostate cancer. Betaine has a number of anticancer effects, such as inactivation of carcinogens, inhibition of cancer cell proliferation, angiogenesis, and metastasis. However, there is no study investigating the effects of betaine on DU-145 cells. The aim of this study was to evaluate the effects of different concentrations of betaine on the oxidative stress, apoptosis, and inflammation on DU-145 cells. Firstly, we proved the cytotoxic activity of betaine (0 to 150 mg/ml) on DU-145 cells by using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and defined the optimal concentration of betaine. Then, by employing the doses found in MTT, the levels of antioxidant (GSH, SOD, CAT, and TAS) and oxidant (MDA and TOS) molecules, pro-inflammatory cytokines (TNF-a and IL-6), apoptotic proteins (CYCS and CASP3), and DNA fragmentation were measured. Morphological changes and apoptosis were evaluated using H&E technique, Bax and Bcl-2 immunohistochemistry. Results suggested that betaine caused oxidative stress, inflammation, inhibition of cell growth, apoptosis, and morphological alterations in DU-145 cells dose-dependently. Furthermore, treatments with increasing betaine concentrations decreased the antioxidant levels in cells. We actually revealed that betaine, known as an antioxidant, may prevent cell proliferation by acting as an oxidant in certain doses. In conclusion, betaine may act as a biological response modifier in prostate cancer treatment in a dose-dependent manner.

Keywords: Apoptosis; Betaine; Cell morphology; DU-145 prostate cancer cell; Oxidative stress.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Betaine / administration & dosage*
  • Betaine / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Male
  • Oxidative Stress / drug effects
  • Prostatic Neoplasms / drug therapy*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Reactive Oxygen Species
  • Betaine