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Oral administration of pyrrolidine dithiocarbamate (PDTC) inhibits VEGF expression, tumor angiogenesis, and growth of breast cancer in female mice.
. 2009 Mar 15; 8(6):514-21.

Abstract

The progression of breast cancer is associated with oxidative stress. However, the effects of pyrrolidine dithiocarbamate (PDTC), a known antioxidant, on the development of breast cancer are poorly understood. The present study evaluates the effects of PDTC on tumor growth, the expression of vascular endothelial growth factor (VEGF), and angiogenesis of breast cancer in female mice. Eight week old female mice (C57BL/6J) were given PDTC at 100 to 200 mg/kg/day for 3 weeks (n=10). The control mice received regular drinking water only. In the 2nd wk, 5x10^5 E0771 (mouse breast cancer) cells were injected in the pad of the fourth mammary gland of the mice. Tumor size was monitored using dial calipers. At the end of the experiment, the tumors were isolated and measured for tumor size, intratumoral microvessel (IM) density using CD31 immunohistochemistry staining, NFκB activation using EMSA, and VEGF protein levels using ELISA. PDTC treatment caused a significant decrease in tumor weight compared to the control (0.64±0.22 vs. 1.43±0.31 g; n=8; P< 0.01), and a significant decrease in IM density (66.1±5.3 vs. 84.2±9.4 IM# /mm^2; P< 0.01). There was a significant decrease in tissue protein levels of VEGF (22.6±2.1 vs. 32.4±2.6 pg/mg) and a 43% reduction NFκB activation in the breast tumors of mice treated with PDTC compared to the control group (P< 0.01). Western blot indicated that estrogen receptor-α (ERα), VEGF receptor-1 (Flt-1), and VEGF receptor-2 (Flk-1) were expressed in E0771 cells. VEGF receptor inhibitor SU5416 and PDTC synergistically suppressed the proliferation of E0771 cells. PDTC also significantly inhibited the migration of cultured E0771 cells. These results support the hypothesis that PDTC suppresses tumor angiogenesis, growth, and migration of breast cancer via inhibiting autocrine and paracrine effects of VEGF through the reduction of NFκB activation and VEGF expression.

Authors+Show Affiliations

Department of Physiology & Biophysics, University of Mississippi Medical Center Jackson, MS 39216, USA. jgu@physiology.umsmedNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19242105

Citation

Gu, Jian-Wei, et al. "Oral Administration of Pyrrolidine Dithiocarbamate (PDTC) Inhibits VEGF Expression, Tumor Angiogenesis, and Growth of Breast Cancer in Female Mice." Cancer Biology & Therapy, vol. 8, no. 6, 2009, pp. 514-21.
Gu JW, Young E, Busby B, et al. Oral administration of pyrrolidine dithiocarbamate (PDTC) inhibits VEGF expression, tumor angiogenesis, and growth of breast cancer in female mice. Cancer Biol Ther. 2009;8(6):514-21.
Gu, J. W., Young, E., Busby, B., Covington, J., & Johnson, J. W. (2009). Oral administration of pyrrolidine dithiocarbamate (PDTC) inhibits VEGF expression, tumor angiogenesis, and growth of breast cancer in female mice. Cancer Biology & Therapy, 8(6), 514-21. https://doi.org/10.4161/cbt.8.6.7689
Gu JW, et al. Oral Administration of Pyrrolidine Dithiocarbamate (PDTC) Inhibits VEGF Expression, Tumor Angiogenesis, and Growth of Breast Cancer in Female Mice. Cancer Biol Ther. 2009 Mar 15;8(6):514-21. PubMed PMID: 19242105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral administration of pyrrolidine dithiocarbamate (PDTC) inhibits VEGF expression, tumor angiogenesis, and growth of breast cancer in female mice. AU - Gu,Jian-Wei, AU - Young,Emily, AU - Busby,Brandi, AU - Covington,Jordan, AU - Johnson,James W, Y1 - 2009/03/15/ PY - 2009/2/27/entrez PY - 2009/2/27/pubmed PY - 2012/10/27/medline SP - 514 EP - 21 JF - Cancer biology & therapy JO - Cancer Biol. Ther. VL - 8 IS - 6 N2 - The progression of breast cancer is associated with oxidative stress. However, the effects of pyrrolidine dithiocarbamate (PDTC), a known antioxidant, on the development of breast cancer are poorly understood. The present study evaluates the effects of PDTC on tumor growth, the expression of vascular endothelial growth factor (VEGF), and angiogenesis of breast cancer in female mice. Eight week old female mice (C57BL/6J) were given PDTC at 100 to 200 mg/kg/day for 3 weeks (n=10). The control mice received regular drinking water only. In the 2nd wk, 5x10^5 E0771 (mouse breast cancer) cells were injected in the pad of the fourth mammary gland of the mice. Tumor size was monitored using dial calipers. At the end of the experiment, the tumors were isolated and measured for tumor size, intratumoral microvessel (IM) density using CD31 immunohistochemistry staining, NFκB activation using EMSA, and VEGF protein levels using ELISA. PDTC treatment caused a significant decrease in tumor weight compared to the control (0.64±0.22 vs. 1.43±0.31 g; n=8; P< 0.01), and a significant decrease in IM density (66.1±5.3 vs. 84.2±9.4 IM# /mm^2; P< 0.01). There was a significant decrease in tissue protein levels of VEGF (22.6±2.1 vs. 32.4±2.6 pg/mg) and a 43% reduction NFκB activation in the breast tumors of mice treated with PDTC compared to the control group (P< 0.01). Western blot indicated that estrogen receptor-α (ERα), VEGF receptor-1 (Flt-1), and VEGF receptor-2 (Flk-1) were expressed in E0771 cells. VEGF receptor inhibitor SU5416 and PDTC synergistically suppressed the proliferation of E0771 cells. PDTC also significantly inhibited the migration of cultured E0771 cells. These results support the hypothesis that PDTC suppresses tumor angiogenesis, growth, and migration of breast cancer via inhibiting autocrine and paracrine effects of VEGF through the reduction of NFκB activation and VEGF expression. SN - 1555-8576 UR - https://www.unboundmedicine.com/medline/citation/19242105/Oral_administration_of_pyrrolidine_dithiocarbamate__PDTC__inhibits_VEGF_expression_tumor_angiogenesis_and_growth_of_breast_cancer_in_female_mice_ L2 - http://www.tandfonline.com/doi/full/10.4161/cbt.8.6.7689 DB - PRIME DP - Unbound Medicine ER -