Sensitization of Radioresistant Prostate Cancer Cells by Resveratrol Isolated from Arachis hypogaea Stems

PLoS One. 2017 Jan 12;12(1):e0169204. doi: 10.1371/journal.pone.0169204. eCollection 2017.

Abstract

Resveratrol (RV, 3,4',5-trihydroxystilbene) is naturally produced by a wide variety of plants including grapes and peanuts (Arachis hypogaea). However, the yield of RV from peanut stem and its potential radiosensitizing effects in prostate cancer (PCa) have not been well investigated. In this study, we characterized RV in peanut stem extract (PSE) for the first time and showed that both RV and PSE dose-dependently induced cell death in DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells with the radioresistant phenotype. Furthermore, the combination of radiation with either RV or PSE induced the death of radioresistant PCa cells through delayed repair of radiation-induced DNA double-strand break (DSB) and prolonged G2/M arrest, which induced apoptosis. The administration of RV and PSE effectively enhanced radiation therapy in the shDAB2IP PCa xenograft mouse model. These results demonstrate the promising synergistic effect of RV and PSE combined with radiation in the treatment of radioresistant PCa.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Arachis / chemistry*
  • Cell Line, Tumor
  • Chemoradiotherapy / methods*
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • G2 Phase Cell Cycle Checkpoints / radiation effects
  • Humans
  • M Phase Cell Cycle Checkpoints / drug effects
  • M Phase Cell Cycle Checkpoints / radiation effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Plant Stems / chemistry*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Radiation Tolerance
  • Resveratrol
  • Stilbenes / chemistry
  • Stilbenes / isolation & purification
  • Stilbenes / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Stilbenes
  • Resveratrol

Grants and funding

This study was supported by grants from Central Taiwan Science Park (103-RB04), Ministry of Science and Technology (104-2911-I-005-501, 104-2320-B-182-040, and 105-2313-B-182-001), Chang Gung Memorial Hospital (CMRPD1F0011-3, CMRPD1F0431-3, and BMRPE90), and the Tomorrow Medical Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.