Lycorine is a novel inhibitor of the growth and metastasis of hormone-refractory prostate cancer

Oncotarget. 2015 Jun 20;6(17):15348-61. doi: 10.18632/oncotarget.3610.

Abstract

Lycorine, a natural alkaloid extracted from the Amaryllidaceae plant family, has been reported to exhibit a wide range of physiological effects, including the potential effect against cancer. However, the anti-prostate cancer (PCa) efficacy of Lycorine remains unrevealed. In this context, we figured out Lycorine's anti-proliferative and anti-migratory properties for PCa treatment. Lycorine inhibited proliferation of various PCa cell lines, induced cell apoptosis and cell death. Here we showed that Lycorine decreased proliferation, migration, invasion, survival and EMT of prostate cancer cell lines. Subcutaneous and orthotopic xenotransplantations by ectopic implantation of the human hormone-refractory PC-3M-luc cells were used to confirm in vivo anticancer effects of Lycorine. Lycorine inhibited both growth and metastasis in multiple organs (liver, lung, kidney, spleen and bone) in vivo and improved mice survival. Lycorine prevented EGF-induced JAK/STAT signaling. Importantly, anti-cancer effects of Lycorine were dependent on STAT expression. We suggest that Lycorine is a potential therapeutic in prostate cancer.

Keywords: STAT3 signaling; hormone-refractory PCa; lycorine; tumor growth and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amaryllidaceae Alkaloids / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Resistance, Neoplasm
  • Epidermal Growth Factor / metabolism*
  • Epithelial-Mesenchymal Transition / drug effects
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Transplantation
  • Phenanthridines / pharmacology*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology*
  • STAT3 Transcription Factor / biosynthesis*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Transplantation, Heterologous

Substances

  • Amaryllidaceae Alkaloids
  • Antineoplastic Agents
  • Phenanthridines
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Epidermal Growth Factor
  • lycorine