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Article

The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development

  • Authors:
    • Candace E. Carroll
    • Yayun Liang
    • Indira Benakanakere
    • Cynthia Besch-Williford
    • Salman M. Hyder
  • View Affiliations / Copyright

    Affiliations: Department of Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211, USA, IDEXX RADIL, Columbia, MO 65201, USA
  • Pages: 179-187
    |
    Published online on: October 24, 2012
       https://doi.org/10.3892/ijo.2012.1675
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Abstract

Recent epidemiological studies show that postmenopausal women taking estrogen-progestin hormone replacement therapy (HRT) have a higher risk of breast cancer than women on an HRT regimen lacking progestins. This may be related to the observation that progestin-treated breast cancer cells express and secrete high levels of vascular endothelial growth factor (VEGF), a potent angiogenic factor that promotes breast tumor growth. Anti-progestins such as RU-486 block this effect, indicating that progesterone receptors (PR) are involved in promoting VEGF induction; however antiprogestins cross-react with other steroid receptors which limits their clinical use. Alternative strategies are, therefore, needed to arrest the growth of progestin-dependent tumors. 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), a novel anticancer drug initially developed as an inhibitor of HIF-1α, is currently undergoing preclinical trials against various forms of cancer. Since HIF-1α has recently been implicated in PR-mediated VEGF synthesis, we undertook studies to determine whether YC-1 inhibits progestin-dependent VEGF induction and tumor progression. Surprisingly, we found that YC-1 downregulated PR in human breast cancer cells, both in vivo and in vitro, thereby blocking progestin-dependent induction of VEGF and tumor growth. YC-1 also inhibited progestin-accelerated DMBA-induced mammary tumors in rats, properties which would likely render it effective against progestin-dependent tumors which frequently develop in post-menopausal women. We, therefore, propose that based on our observations, YC-1 warrants further investigation as a novel agent which could prove extremely useful as an anti-angiogenic chemotherapeutic drug.
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View References

1. 

Ross R, Paganini-Hill A and Pike MC: Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. J Natl Cancer Inst. 92:328–332. 2000. View Article : Google Scholar

2. 

Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L and Hoover R: Menopausal estrogen and estrogen progestin replacement therapy and breast cancer risk. JAMA. 283:485–491. 2000. View Article : Google Scholar : PubMed/NCBI

3. 

Li CI, Malone KE, Porter PL, Weiss NS, Tang MT, Cushing-Haugen KL and Daling JR: Relationship between long durations and different regimens of hormone therapy and risk of breast cancer. JAMA. 289:3254–3263. 2003. View Article : Google Scholar : PubMed/NCBI

4. 

Chlebowski RT, Anderson GL, Gass M, Lane DS, Aragaki AK, Kuller LH, Manson JE, Stefanick ML, Ockene J, Sarto GE, Johnson KC, Wactawski-Wende J, Ravdin PM, Schenken R, Hendrix SL, Rajkovic A, Rohan TE, Yasmeen S and Prentice RL; WHI Investigators: Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA. 304:1684–1692. 2010. View Article : Google Scholar : PubMed/NCBI

5. 

Liang Y, Wu J, Stancel GM and Hyder SM: p53-dependent inhibition of progestin-induced VEGF expression in human breast cancer cells. J Steroid Biochem Mol Biol. 93:173–182. 2005. View Article : Google Scholar : PubMed/NCBI

6. 

Liang Y and Hyder SM: Proliferation of endothelial and tumor epithelial cells by progestin-induced vascular endothelial growth factor from human breast cancer cells: paracrine and autocrine effects. Endocrinology. 146:3632–3641. 2005. View Article : Google Scholar

7. 

Benakanakere I, Besch-Williford C, Schnell J, Brandt S, Ellersieck MR, Molinolo A and Hyder SM: Natural and synthetic progestins accelerate 7,12-dimethylbenz[a]anthracene-initiated mammary tumors and increase angiogenesis in Sprague-Dawley rats. Clin Cancer Res. 12:4062–4071. 2006.PubMed/NCBI

8. 

Liang Y, Besch-Williford C, Brekken RA and Hyder SM: Progestin-dependent progression of human breast tumor xenografts: a novel model for evaluating antitumor theraputics. Cancer Res. 67:9929–9936. 2007. View Article : Google Scholar : PubMed/NCBI

9. 

Horwitz K: The molecular biology of RU-486. Is there a role for anti-progestins in the treatment of breast cancer? Endocr Rev. 12:146–163. 1992.PubMed/NCBI

10. 

Otrock ZK, Hatoum HA, Awada AH, Ishak RS and Shamseddine AI: Hypoxia-inducible factor in cancer angiogenesis: structure, regulation and clinical perspectives. Crit Rev Oncol Hematol. 70:93–102. 2009. View Article : Google Scholar : PubMed/NCBI

11. 

Carmeliet P, Dor Y, Herbert J-M, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, Koch CJ, Ratcliffe P, Moons L, Jain RK, Collen D and Keshet E: Role of HIF-1[alpha] in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature. 394:485–490. 1998.

12. 

Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD and Semenza GL: Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 16:4604–4613. 1996.PubMed/NCBI

13. 

Shimizu T and Miyamoto A: Progesterone induces the expression of vascular endothelial growth factor (VEGF) 120 and Flk-1, its receptor, in bovine granulose cells. Anim Reprod Sci. 102:228–237. 2007. View Article : Google Scholar : PubMed/NCBI

14. 

Semenza GL: HIF-1: using two hands to flip the angiogenic switch. Cancer Metastasis Rev. 19:59–65. 2000. View Article : Google Scholar : PubMed/NCBI

15. 

Chun YS, Yeo EJ, Choi E, Teng CM, Bae JM, Kim MS and Park JW: Inhibitory effect of YC-1 on the hypoxic induction of erythropoietin and vascular endothelial growth factor in Hep3B cells. Biochem Pharmacol. 61:947–954. 2001. View Article : Google Scholar : PubMed/NCBI

16. 

Tulis DA, Durante W, Peyton KJ, Chapman GB, Evans AJ and Schafer AI: YC-1, a benzyl indazole derivative, stimulates vascular cGMP and inhibits neointima formation. Biochem Biophys Res Commun. 279:646–652. 2000. View Article : Google Scholar : PubMed/NCBI

17. 

Huang YT, Pan SL, Guh JH, Chang YL, Lee FY, Kuo SC and Teng CM: YC-1 suppresses constitutive nuclear factor-kappaB activation and induces apoptosis in human prostate cancer cells. Mol Cancer Ther. 4:1628–1635. 2005. View Article : Google Scholar

18. 

Yeo E-J, Chun YS, Cho YS, Kim J, Lee J-C, Kim M-S and Park J-W: YC-1: A potential anticancer drug targeting hypoxiainducible factor 1. J Natl Cancer Inst. 95:516–525. 2003. View Article : Google Scholar : PubMed/NCBI

19. 

Rubinstein LV, Shoemaker RH, Paull KD, Simon RM, Tosini S, Skehan P, Scudiero DA, Monks A and Boyd MR: Comparison of in vitro anticancer-drug-screening data generated with a tetrazolium assay versus a protein assay against a diverse panel of human tumor cell lines. J Natl Cancer Inst. 82:1113–1118. 1990. View Article : Google Scholar : PubMed/NCBI

20. 

Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S and Boyd MR: New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 82:1107–1112. 1990. View Article : Google Scholar : PubMed/NCBI

21. 

Carroll CE, Ellersieck MR and Hyder SM: Curcumin inhibits MPA-induced secretion of VEGF from T47-D human breast cancer cells. Menopause. 15:570–574. 2008. View Article : Google Scholar

22. 

Hyder S, Murthry L and Stancel GM: Progestin regulation of vascular endothelial growth factor in human breast cancer cells. Cancer Res. 58:392–395. 1998.PubMed/NCBI

23. 

Mafuvadze B, Benakanakere I and Hyder SM: Apigenin blocks induction of vascular endothelial growth factor mRNA and protein in progestin-treated human breast cancer cells. Menopause. 17:1055–1063. 2010. View Article : Google Scholar : PubMed/NCBI

24. 

Benakanakere I, Besch-Williford C, Ellersieck MR and Hyder SM: Regression of progestin-accelerated 7,12-dimethylbenz[a] anthracene-induced mammary tumors in Sprague-Dawley rats by p53 reactivation and induction of massive apoptosis: a pilot study. Endocr Relat Cancer. 16:85–98. 2009.PubMed/NCBI

25. 

Conover W and Iman RL: Rank transformations as a bridge between parametric and nonparametric statistics. Am Stat. 35:124–129. 1981.

26. 

Chew V: Comparison among treatment means and analysis of variance. Agricultural Research Service, USDA (ARS/H/6 Report); Washington, DC: pp. 32–35. 1977

27. 

Liang Y, Benakanakere I, Besch-Williford C, Hyder RS, Ellersieck MR and Hyder SM: Synthetic progestins induce growth and metastasis of BT-474 human breast cancer xenografts in nude mice. Menopause. 17:1040–1047. 2010. View Article : Google Scholar : PubMed/NCBI

28. 

Dennis AP, Lonard DM, Nawaz Z and O’Malley BW: Inhibition of the 26S proteasome blocks progesterone receptor-dependent transcription through failed recruitment of RNA polymerase II. J Steroid Biochem Mol Biol. 94:337–346. 2005. View Article : Google Scholar

29. 

Hyder SM, Chiappetta C and Stancel GM: Pharmacological and endogenous progestins induce vascular endothelial growth factor expression in human breast cancer cells. Int J Cancer. 92:469–473. 2001. View Article : Google Scholar : PubMed/NCBI

30. 

Rundqvist H and Johnson RS: Hypoxia and metastasis in breast cancer. Curr Top Microbiol Immunol. 345:121–139. 2010.PubMed/NCBI

31. 

Kazi A, Jones JM and Koos RD: Chromatin immunoprecipitation analysis of gene expression in the rat uterus in vivo: estrogen-induced recruitment of both estrogen receptor α and hypoxia-inducible factor 1 to the vascular endothelial growth factor promoter. Mol Endocrinol. 19:2006.–2019. 2005.

32. 

Pan SL, Guh JH, Peng CY, Wang SW, Chang YL, Cheng FC, Chang JH, Kuo SC, Lee FY and Teng CM: YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyindazole] inhibits endothelial cell functions induced by angiogenic factors in vitro and angiogenesis in vivo models. J Pharmacol Exp Ther. 314:35–42. 2005.

33. 

Liang Y, Besch-Williford C, Benakanakere I, Thorpe PE and Hyder SM: Targeting mutant p53 protein and the tumor vasculature: an effective combination therapy for advanced breast tumors. Breast Cancer Res Treat. 125:407–420. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Carroll CE, Liang Y, Benakanakere I, Besch-Williford C and Hyder SM: The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development. Int J Oncol 42: 179-187, 2013.
APA
Carroll, C.E., Liang, Y., Benakanakere, I., Besch-Williford, C., & Hyder, S.M. (2013). The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development. International Journal of Oncology, 42, 179-187. https://doi.org/10.3892/ijo.2012.1675
MLA
Carroll, C. E., Liang, Y., Benakanakere, I., Besch-Williford, C., Hyder, S. M."The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development". International Journal of Oncology 42.1 (2013): 179-187.
Chicago
Carroll, C. E., Liang, Y., Benakanakere, I., Besch-Williford, C., Hyder, S. M."The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development". International Journal of Oncology 42, no. 1 (2013): 179-187. https://doi.org/10.3892/ijo.2012.1675
Copy and paste a formatted citation
x
Spandidos Publications style
Carroll CE, Liang Y, Benakanakere I, Besch-Williford C and Hyder SM: The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development. Int J Oncol 42: 179-187, 2013.
APA
Carroll, C.E., Liang, Y., Benakanakere, I., Besch-Williford, C., & Hyder, S.M. (2013). The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development. International Journal of Oncology, 42, 179-187. https://doi.org/10.3892/ijo.2012.1675
MLA
Carroll, C. E., Liang, Y., Benakanakere, I., Besch-Williford, C., Hyder, S. M."The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development". International Journal of Oncology 42.1 (2013): 179-187.
Chicago
Carroll, C. E., Liang, Y., Benakanakere, I., Besch-Williford, C., Hyder, S. M."The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development". International Journal of Oncology 42, no. 1 (2013): 179-187. https://doi.org/10.3892/ijo.2012.1675
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