Antrocin sensitizes prostate cancer cells to radiotherapy through inhibiting PI3K/AKT and MAPK signaling pathways

Yu An Chen, David T.W. Tzeng, Yi Ping Huang, Chun Jung Lin, U. Ging Lo, Chia Lin Wu, Ho Lin, Jer Tsong Hsieh, Chih Hsin Tang, Chih Ho Lai

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Radiotherapy is one of the most common treatment options for local or regional advanced prostate cancer (PCa). Importantly, PCa is prone to radioresistance and often develops into malignancies after long-term radiotherapy. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, possesses pharmacological efficacy against various cancer types; however, its therapeutic potential requires comprehensive exploration, particularly in radioresistant PCa cells. In this study, we emphasized the effects of antrocin on radioresistant PCa cells and addressed the molecular mechanism underlying the radiosensitization induced by antrocin. Our results showed that a combination treatment with antrocin and ionizing radiation (IR) synergistically inhibited cell proliferation and induced apoptosis in radioresistant PCa cells. We further demonstrated that antrocin downregulated PI3K/AKT andMAPK signaling pathways as well as suppressed type 1 insulin-like growth factor 1 receptor (IGF-1R)-mediated induction of β-catenin to regulate cell cycle and apoptosis. Using xenograft mouse models, we showed that antrocin effectively enhanced radiotherapy in PCa. Our study demonstrates that antrocin sensitizes PCa to radiation through constitutive suppression of IGF-1R downstream signaling, revealing that it can be developed as a potent therapeutic agent to overcome radioresistant PCa.

Original languageEnglish (US)
Article number34
JournalCancers
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • Antrocin
  • Prostate cancer
  • Radioresistance
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Antrocin sensitizes prostate cancer cells to radiotherapy through inhibiting PI3K/AKT and MAPK signaling pathways'. Together they form a unique fingerprint.

  • Cite this

    Chen, Y. A., Tzeng, D. T. W., Huang, Y. P., Lin, C. J., Lo, U. G., Wu, C. L., Lin, H., Hsieh, J. T., Tang, C. H., & Lai, C. H. (2019). Antrocin sensitizes prostate cancer cells to radiotherapy through inhibiting PI3K/AKT and MAPK signaling pathways. Cancers, 11(1), [34]. https://doi.org/10.3390/cancers11010034