Apoptotic markers in a prostate cancer cell line: effect of ellagic acid

Oncol Rep. 2013 Dec;30(6):2804-10. doi: 10.3892/or.2013.2757. Epub 2013 Sep 30.

Abstract

Ellagic acid (EA) inhibits cell growth and induces apoptosis in cultured cells; however, the precise molecular mechanism involved in EA-induced apoptosis in prostate cancer cells is unknown. The aim of the present study was to delineate possible apoptotic pathway(s) involved in the EA-mediated chemotherapeutic effects in the LNCaP human prostatic cancer cell line. EA produced anti-proliferative effects through inhibition of rapamycin (mTOR) activation and a reduction in intracellular levels of β-catenin. Moreover, we demonstrated that EA induced apoptosis via downregulation of the anti-apoptotic proteins, silent information regulator 1 (SIRT1), human antigen R (HuR) and heme oxygenase-1 (HO-1). EA modulated the expression of apoptosis-inducing factor (AIF) resulting in a significant increase in reactive oxygen species (ROS) levels and the activation of caspase-3. Finally, we demonstrated that EA reduced both transforming growth factor-β (TGF-β) and interleukin-6 (IL-6) levels. EA treatment resulted in the increased expression of the tumor suppressor protein p21 and increased the percentage of apoptotic cells. In conclusion, the results suggest that EA treatment represents a new and highly effective strategy in reducing prostate cancer carcinogenesis.

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / biosynthesis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Ellagic Acid / administration & dosage*
  • Gene Expression Regulation, Neoplastic
  • Heme Oxygenase-1 / biosynthesis
  • Humans
  • Interleukin-6 / biosynthesis
  • Male
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Reactive Oxygen Species / metabolism
  • beta Catenin / biosynthesis

Substances

  • Interleukin-6
  • Reactive Oxygen Species
  • beta Catenin
  • Ellagic Acid
  • Heme Oxygenase-1
  • Caspase 3