Cell killing and radiosensitizing effects of atorvastatin in PC3 prostate cancer cells

Zhenhua He, Lingegowda S. Mangala, Corey A. Theriot, Larry H. Rohde, Honglu Wu, Ye Zhang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Recent studies have indicated that autophagy may be one of the important pathways induced by ionizing radiation. Atorvastatin (statin), an inhibitor of 3-hydroxyl-3-methylglutaryl coenzyme A (HMGCoA) reductase, may exhibit anticancer effects as an autophagy inducer. In our study, the cell killing and radiosensitizing effects of statin were analyzed in PC3 cell line. Activation of the autophagy pathway was analyzed using the GFP-LC3 assay and western blot to determine LC3-II expression. The radiosensitivity of PC3 cells was determined using the clonal survival assay, TUNEL assay, and the Annexin V apoptosis assay. The expression profiles of autophagy related genes were analyzed using a pathway specific realtime polymerase chain reaction (PCR) array. Autophagic response was induced in PC3 cells after exposure to statin and/or gamma rays. Inhibition of the autophagic process using small interfering RNAs (siRNA) targeting Atg7 and/or Atgl2 significantly reduced radiosensitivity of PC3 cells. Statin also exhibited a significant apoptosis-inducing effect in PC3 cells, which can be partially suppressed by Atg7 siRNA. Cells treated with statin and gamma irradiation showed significantly reduced colony forming efficiency and increased number of Annexin V positive early apoptotic cells. Analysis of autophagy and its regulatory gene profile showed that the expressions of 22 genes out of 86 genes assessed were significantly altered in the cells exposed to combined treatment or statin alone. The data indicate that activation of the autophagy pathway may be responsible for apoptosis inducing effect of statin. Furthermore, combined treatment with radiation and autophagic inducer, such as statin, may be synergistic in inducing cell death of PC3 cells.

Original languageEnglish (US)
Pages (from-to)225-233
Number of pages9
JournalJournal of Radiation Research
Volume53
Issue number2
DOIs
StatePublished - Mar 2012
Externally publishedYes

Fingerprint

Radiation-Sensitizing Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Prostatic Neoplasms
cancer
Autophagy
genes
cells
apoptosis
radiation tolerance
Annexin A5
Radiation Tolerance
Apoptosis
Small Interfering RNA
activation
coenzymes
polymerase chain reaction
profiles
Atorvastatin Calcium
cultured cells
death

Keywords

  • Gamma rays
  • PC3 cells
  • Prostate cancer
  • Radiosensitivity
  • Statin

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Health, Toxicology and Mutagenesis

Cite this

He, Z., Mangala, L. S., Theriot, C. A., Rohde, L. H., Wu, H., & Zhang, Y. (2012). Cell killing and radiosensitizing effects of atorvastatin in PC3 prostate cancer cells. Journal of Radiation Research, 53(2), 225-233. https://doi.org/10.1269/jrr.11114

Cell killing and radiosensitizing effects of atorvastatin in PC3 prostate cancer cells. / He, Zhenhua; Mangala, Lingegowda S.; Theriot, Corey A.; Rohde, Larry H.; Wu, Honglu; Zhang, Ye.

In: Journal of Radiation Research, Vol. 53, No. 2, 03.2012, p. 225-233.

Research output: Contribution to journalArticle

He, Z, Mangala, LS, Theriot, CA, Rohde, LH, Wu, H & Zhang, Y 2012, 'Cell killing and radiosensitizing effects of atorvastatin in PC3 prostate cancer cells', Journal of Radiation Research, vol. 53, no. 2, pp. 225-233. https://doi.org/10.1269/jrr.11114
He, Zhenhua ; Mangala, Lingegowda S. ; Theriot, Corey A. ; Rohde, Larry H. ; Wu, Honglu ; Zhang, Ye. / Cell killing and radiosensitizing effects of atorvastatin in PC3 prostate cancer cells. In: Journal of Radiation Research. 2012 ; Vol. 53, No. 2. pp. 225-233.
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