Skip to main content

Relationship of oral glycine with radiation-induced HIF1-alpha and tumor growth delay in a prostate cancer xenograft.

Publication ,  Journal Article
Su, LJ; Yang, X; Altunbas, C; Flaig, TW; Li, CY; Kavanagh, BD
Published in: J Clin Oncol
February 20, 2013

81 Background: Preclinical studies have shown that nitric oxide (NO) is produced by upregulation of inducible nitric oxide synthase (iNOS) in activated macrophages recruited to the site of cytotoxic injury from radiation or chemotherapy. NO stabilizes hypoxia-inducible factor 1-alpha (HIF1α), leading to increased vascular endothelial growth factor, thus promoting tumor angiogenesis as a recovery mechanism from the initial cytotoxic insult. Because glycine (G) suppresses macrophage activation, we hypothesized that dietary supplementation with G would inhibit HIF1α expression and enhance tumor growth delay by preventing recovery angiogenesis. METHODS: PC3 cells were transfected with a HIF1α-inducible luciferase reporter and grown as nude mice xenografts. As tumors grew to 100mm(3), mice were continued in 1 of 4 conditions: 1) control (C) diet ; 2) a 5%G diet; 3) C diet with ad libitum drinking water treated with L-NAME (500mg/L), an iNOS inhibitor; or 4) C diet with a single injection of carrageenan (2mg/500uL), a selective macrophagicidal agent. After 3 days tumors were irradiated with 0 Gy (sham) or 6 Gy using a 160kV source. Tumor growth and quantitative bioluminescence data were then collected (n = 4 mice/group). RESULTS: HIF1α expression as assessed by bioluminescence increased more than two fold 4-6 days after 6 Gy (p<0.05) in the C diet group but did not significantly increase in either the L-NAME, 5%G , or carrageenan groups. Tumor growth curves for the 6 Gy L-NAME and 5%G diet groups showed a corresponding statistically significant growth delay compared to 6 Gy C diet. No clear difference in bioluminescence or growth was noted in any 0 Gy cohort. CONCLUSIONS: The results support the hypothesis that radiation injury indirectly upregulates HIF1α via an iNOS dependent pathway. Inhibition of this pathway can enhance in vivo radiation-induced tumor growth delay and can be achieved via dietary supplementation with G. Thus, dietary G supplementation might have a clinical role for patients treated with radiotherapy for prostate cancer as a non-toxic means of achieving radiosensitization.

Duke Scholars

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

February 20, 2013

Volume

31

Issue

6_suppl

Start / End Page

81

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Su, L. J., Yang, X., Altunbas, C., Flaig, T. W., Li, C. Y., & Kavanagh, B. D. (2013). Relationship of oral glycine with radiation-induced HIF1-alpha and tumor growth delay in a prostate cancer xenograft. J Clin Oncol, 31(6_suppl), 81. https://doi.org/10.1200/jco.2013.31.6_suppl.81
Su, L. J., X. Yang, C. Altunbas, T. W. Flaig, C. Y. Li, and B. D. Kavanagh. “Relationship of oral glycine with radiation-induced HIF1-alpha and tumor growth delay in a prostate cancer xenograft.J Clin Oncol 31, no. 6_suppl (February 20, 2013): 81. https://doi.org/10.1200/jco.2013.31.6_suppl.81.
Su LJ, Yang X, Altunbas C, Flaig TW, Li CY, Kavanagh BD. Relationship of oral glycine with radiation-induced HIF1-alpha and tumor growth delay in a prostate cancer xenograft. J Clin Oncol. 2013 Feb 20;31(6_suppl):81.
Su, L. J., et al. “Relationship of oral glycine with radiation-induced HIF1-alpha and tumor growth delay in a prostate cancer xenograft.J Clin Oncol, vol. 31, no. 6_suppl, Feb. 2013, p. 81. Pubmed, doi:10.1200/jco.2013.31.6_suppl.81.
Su LJ, Yang X, Altunbas C, Flaig TW, Li CY, Kavanagh BD. Relationship of oral glycine with radiation-induced HIF1-alpha and tumor growth delay in a prostate cancer xenograft. J Clin Oncol. 2013 Feb 20;31(6_suppl):81.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

February 20, 2013

Volume

31

Issue

6_suppl

Start / End Page

81

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences