Simvastatin sensitizes radioresistant prostate cancer cells by compromising DNA double-strand break repair

Yu An Chen, Hua Wei Shih, Yi Chun Lin, Hui Ying Hsu, Tsu Fang Wu, Chen Han Tsai, Chia Lin Wu, Hui Yu Wu, Jer Tsong Hsieh, Chih Hsin Tang, Chih Ho Lai

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Prostate cancer (PCa) is one of the most prevalent male cancers in western world. Radiation therapy (RT) is commonly used to treat PCa patients. However, a certain proportion of patients develop radioresistant PCa cells, which results in metastatic disease. Statins, which inhibit 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, are commonly used to treat hypercholesterolemia, exhibiting beneficial effects on cardiovascular diseases and on several types of cancers, including PCa. However, the mechanistic details and crosstalk between statins and RT in PCa cells remain unknown. In this study, radioresistant DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells were used to evaluate whether simvastatin could enhance the effect of ionizing radiation (IR). The crucial molecules that associated with simvastatin elevated radiosensitivity in PCa cells were explored. Our results demonstrated that a combination treatment with simvastatin and IR synergistically induced apoptosis of radioresistant PCa cells. In addition, simvastatin appeared to compromise DNA double-strand breaks repair by activating the expressions of histone 2A family member X (γ-H2AX) and phospho-checkpoint kinase 1 (p-CHK1), suggesting an underlying mechanism for this radiosensitization of PCa cells. These findings reveal that simvastatin may be a potent therapeutic agent for co-treatment with radiation to overcome radioresistance in PCa cells.

Original languageEnglish (US)
Article number600
JournalFrontiers in Pharmacology
Volume9
Issue numberJUN
DOIs
StatePublished - Jun 13 2018

Fingerprint

Simvastatin
Double-Stranded DNA Breaks
Prostatic Neoplasms
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Ionizing Radiation
Radiotherapy
Western World
Radiation Tolerance
Hypercholesterolemia
Histones
Oxidoreductases
Cardiovascular Diseases
Therapeutics
Radiation
Apoptosis

Keywords

  • Cholesterol
  • DNA double-strand break
  • HMG-CoA reductase
  • Prostate cancer
  • Radioresistance
  • Simvastatin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Chen, Y. A., Shih, H. W., Lin, Y. C., Hsu, H. Y., Wu, T. F., Tsai, C. H., ... Lai, C. H. (2018). Simvastatin sensitizes radioresistant prostate cancer cells by compromising DNA double-strand break repair. Frontiers in Pharmacology, 9(JUN), [600]. https://doi.org/10.3389/fphar.2018.00600

Simvastatin sensitizes radioresistant prostate cancer cells by compromising DNA double-strand break repair. / Chen, Yu An; Shih, Hua Wei; Lin, Yi Chun; Hsu, Hui Ying; Wu, Tsu Fang; Tsai, Chen Han; Wu, Chia Lin; Wu, Hui Yu; Hsieh, Jer Tsong; Tang, Chih Hsin; Lai, Chih Ho.

In: Frontiers in Pharmacology, Vol. 9, No. JUN, 600, 13.06.2018.

Research output: Contribution to journalArticle

Chen, YA, Shih, HW, Lin, YC, Hsu, HY, Wu, TF, Tsai, CH, Wu, CL, Wu, HY, Hsieh, JT, Tang, CH & Lai, CH 2018, 'Simvastatin sensitizes radioresistant prostate cancer cells by compromising DNA double-strand break repair', Frontiers in Pharmacology, vol. 9, no. JUN, 600. https://doi.org/10.3389/fphar.2018.00600
Chen, Yu An ; Shih, Hua Wei ; Lin, Yi Chun ; Hsu, Hui Ying ; Wu, Tsu Fang ; Tsai, Chen Han ; Wu, Chia Lin ; Wu, Hui Yu ; Hsieh, Jer Tsong ; Tang, Chih Hsin ; Lai, Chih Ho. / Simvastatin sensitizes radioresistant prostate cancer cells by compromising DNA double-strand break repair. In: Frontiers in Pharmacology. 2018 ; Vol. 9, No. JUN.
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