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Article

Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis

  • Authors:
    • Jiumao Lin
    • Lihui Wei
    • Aling Shen
    • Qiaoyan Cai
    • Wei Xu
    • Huang Li
    • Youzhi Zhan
    • Zhenfeng Hong
    • Jun Peng
  • View Affiliations / Copyright

    Affiliations: Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Minhou Shangjie, Fuzhou, Fujian 350122, P.R. China, Department of Pharmacology, Fujian University of Traditional Chinese Medicine, Minhou Shangjie, Fuzhou, Fujian 350122, P.R. China
  • Pages: 651-656
    |
    Published online on: December 27, 2012
       https://doi.org/10.3892/ijo.2012.1753
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Abstract

Sonic hedgehog (SHH) signaling pathway promotes the process of angiogenesis, contributing to the growth and progression of many human malignancies including colorectal cancer (CRC), which therefore has become a promising target for cancer chemotherapy. Hedyotis diffusa Willd (HDW), as a well-known traditional Chinese herbal medicine, has long been used in China for the clinic treatment of various cancers. Recently, we reported that HDW can inhibit colorectal cancer growth in vivo and in vitro via suppression of the STAT3 pathway. In addition, we demonstrated the anti-angiogenic activity of HDW in vitro. To further elucidate the mechanism of the tumoricidal activity of HDW, by using a CRC mouse xenograft model we evaluated the in vivo effect of the ethanol extract of HDW (EEHDW) on tumor angiogenesis, and investigated the underlying molecular mechanisms. We found that EEHDW could significantly reduce intratumoral microvessel density (MVD), indicating its activity of antitumor angiogenesis in vivo. EEHDW suppressed the activation of SHH signaling in CRC xenograft tumors since it significantly decreased the expression of key mediators of SHH pathway. EEHDW treatment inhibited the expression of the critical SHH signaling target gene VEGF-A as well as its specific receptor VEGFR2. Taken together, we propose for the first time that Hedyotis diffusa Willd inhibits colorectal cancer growth in vivo via inhibition of SHH-mediated tumor angiogenesis.
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1. 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar

2. 

Gustin DM and Brenner DE: Chemoprevention of colon cancer: current status and future prospects. Cancer Metast Rev. 21:323–348. 2002. View Article : Google Scholar : PubMed/NCBI

3. 

Lin J, Chen Y, Wei L, Chen X, Xu W, Hong Z, Sferra TJ and Peng J: Hedyotis diffusa Willd extract induces apoptosis via activation of the mitochondrion-dependent pathway in human colon carcinoma cells. Int J Oncol. 37:1331–1338. 2010.

4. 

Gordaliza M: Natural products as leads to anticancer drugs. Clin Transl Oncol. 9:767–776. 2007. View Article : Google Scholar : PubMed/NCBI

5. 

Ji HF, Li XJ and Zhang HY: Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO Rep. 10:194–200. 2009.PubMed/NCBI

6. 

Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med. 285:1182–1186. 1971. View Article : Google Scholar : PubMed/NCBI

7. 

Folkman J: Angiogenesis. Annu Rev Med. 57:1–18. 2006. View Article : Google Scholar

8. 

Cook KM and Figg WD: Angiogenesis inhibitors: current strategies and future prospects. CA Cancer J Clin. 60:222–243. 2010. View Article : Google Scholar : PubMed/NCBI

9. 

Ingham PW, Nakano Y and Seger C: Mechanisms and functions of Hedgehog signalling across the metazoa. Nat Rev Genet. 12:393–406. 2011. View Article : Google Scholar : PubMed/NCBI

10. 

Zhang S, Wang Y, Mao JH, Hsieh D, Kim IJ, Hu LM, Xu Z, Long H, Jablons DM and You L: Inhibition of CK2α down-regulates Hedgehog/Gli signaling leading to a reduction of a stem-like side population in human lung cancer cells. PLoS One. 7:e389962012.

11. 

Theunissen JW and de Sauvage FJ: Paracrine Hedgehog signaling in cancer. Cancer Res. 69:6007–6010. 2009. View Article : Google Scholar : PubMed/NCBI

12. 

Mazumdar T, DeVecchio J, Shi T, Jones J, Agyeman A and Houghton JA: Hedgehog signaling drives cellular survival in human colon carcinoma cells. Cancer Res. 71:1092–1102. 2011. View Article : Google Scholar : PubMed/NCBI

13. 

Yoshikawa K, Shimada M, Miyamoto H, Higashijima J, Miyatani T, Nishioka M, Kurita N, Iwata T and Uehara H: Sonic hedgehog relates to colorectal carcinogenesis. J Gastroenterol. 44:1113–1117. 2009. View Article : Google Scholar : PubMed/NCBI

14. 

Varnat F, Duquet A, Malerba M, Zbinden M, Mas C, Gervaz P and Ruiz i Altaba A: Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med. 1:338–351. 2009. View Article : Google Scholar

15. 

Das S, Tucker JA, Khullar S, Samant RS and Shevde LA: Hedgehog signaling in tumor cells facilitates osteoblast-enhanced osteolytic metastases. PLoS One. 7:e343742012. View Article : Google Scholar : PubMed/NCBI

16. 

Sahebjam S, Siu LL and Razak AA: The utility of Hedgehog signaling pathway inhibition for cancer. Oncologist. 17:1090–1099. 2012. View Article : Google Scholar : PubMed/NCBI

17. 

Wei L, Lin J, Xu W, Cai Q, Shen A, Hong Z and Peng J: Scutellaria barbata D. Don inhibits tumor angiogenesis via suppression of Hedgehog pathway in a mouse model of colorectal cancer. Int J Mol Sci. 13:9419–9430. 2012. View Article : Google Scholar

18. 

Lum L and Beachy PA: The Hedgehog response network: sensors, switches, and routers. Science. 304:1755–1759. 2004. View Article : Google Scholar : PubMed/NCBI

19. 

Varjosalo M and Taipale J: Hedgehog: functions and mechanisms. Genes Dev. 22:2454–2472. 2008. View Article : Google Scholar : PubMed/NCBI

20. 

Pola R, Ling LE, Silver M, Corbley MJ, Kearney M, Pepinsky RB, Shapiro R, Taylor FR, Baker DP and Asahara T: The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors. Nat Med. 7:706–711. 2001. View Article : Google Scholar : PubMed/NCBI

21. 

Claret S, Sanial M and Plessis A: Evidence for a novel feedback loop in the Hedgehog pathway involving smoothened and fused. Curr Biol. 17:1326–1333. 2007. View Article : Google Scholar : PubMed/NCBI

22. 

Kerbel RS: Tumor angiogenesis. N Engl J Med. 358:2039–2049. 2008. View Article : Google Scholar : PubMed/NCBI

23. 

Prasad S, Yadav VR, Sung B, Reuter S, Kannappan R, Deorukhkar A, Diagaradjane P, Wei C, Baladandayuthapani V, Krishnan S, Guha S and Aggarwal BB: Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine. Clin Cancer Res. 18:4942–4953. 2012. View Article : Google Scholar

24. 

Dai J, Wan S, Zhou F, Myers RE, Guo X, Li B, Fu X, Palazzo JP, Dou K, Yang H and Xing J: Genetic polymorphism in a VEGF-independent angiogenesis gene ANGPT1 and overall survival of colorectal cancer patients after surgical resection. PLoS One. 7:e347582012. View Article : Google Scholar

25. 

Lin J, Wei L, Xu W, Hong Z, Liu X and Peng J: Effect of Hedyotis diffusa Willd extract on tumor angiogenesis. Mol Med Rep. 4:1283–1288. 2011.

26. 

Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI

27. 

Shigami SI, Arii S, Furutani M, Niwano M, Harada T, Mizumoto M, Mori A, Onodera H and Imamura M: Predictive value of vascular endothelial growth factor (VEGF) in metastasis and prognosis of human colorectal cancer. Br J Cancer. 78:1379–1384. 1998. View Article : Google Scholar : PubMed/NCBI

28. 

Gille H, Kowalski J, Li B, LeCouter J, Moffat B, Zioncheck TF, Pelletier N and Ferrara N: Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J Biol Chem. 276:3222–3230. 2001. View Article : Google Scholar

29. 

Ferrara N: Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: therapeutic implications. Semin Oncol. 29:10–14. 2002. View Article : Google Scholar : PubMed/NCBI

30. 

Risau W: Mechanisms of angiogenesis. Nature. 386:671–674. 1997. View Article : Google Scholar : PubMed/NCBI

31. 

Ren F, Liu G, Zhang L and Niu G: Studies on chemical constituents of Hedyotis diffusa Willd. Chin Pharm J. 40:502–504. 2005.

32. 

Ahmad R, Shaari K, Lajis NH, Hamzah AS, Ismail NH and Kitajima M: Anthraquinones from Hedyotis capitellata. Phytochemistry. 66:1141–1147. 2005. View Article : Google Scholar : PubMed/NCBI

33. 

Li C, Xue X, Zhou D, Zhang F, Xu Q, Ren L and Liang X: Analysis of iridoid glucosides in Hedyotis diffusa by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. J Pharm Biomed Anal. 48:205–211. 2008.

34. 

Cai Q, Lin J, Wei L, Zhang L, Wang L, Zhan Y, Zeng J, Xu W, Shen A, Hong Z and Peng J: Hedyotis diffusa Willd inhibits colorectal cancer growth in vivo via inhibition of STAT3 signaling pathway. Int J Mol Sci. 13:6117–6128. 2012. View Article : Google Scholar

35. 

Chen HX and Cleck JN: Adverse effects of anticancer agents that target the VEGF pathway. Nat Rev Clin Oncol. 6:465–477. 2009. View Article : Google Scholar : PubMed/NCBI

36. 

Zangari M, Fink LM, Elice F, Zhan F, Adcock DM and Tricot GJ: Thrombotic events in patients with cancer receiving antiangiogenesis agents. J Clin Oncol. 27:4865–4873. 2009. View Article : Google Scholar : PubMed/NCBI

37. 

Higa GM and Abraham J: Biological mechanisms of bevacizumab-associated adverse events. Expert Rev Anticancer Ther. 9:999–1007. 2009. View Article : Google Scholar : PubMed/NCBI

38. 

Jain RK: Tumor angiogenesis and accessibility: role of vascular endothelial growth factor. Semin Oncol. 29:3–9. 2002. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lin J, Wei L, Shen A, Cai Q, Xu W, Li H, Zhan Y, Hong Z and Peng J: Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis. Int J Oncol 42: 651-656, 2013.
APA
Lin, J., Wei, L., Shen, A., Cai, Q., Xu, W., Li, H. ... Peng, J. (2013). Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis. International Journal of Oncology, 42, 651-656. https://doi.org/10.3892/ijo.2012.1753
MLA
Lin, J., Wei, L., Shen, A., Cai, Q., Xu, W., Li, H., Zhan, Y., Hong, Z., Peng, J."Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis". International Journal of Oncology 42.2 (2013): 651-656.
Chicago
Lin, J., Wei, L., Shen, A., Cai, Q., Xu, W., Li, H., Zhan, Y., Hong, Z., Peng, J."Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis". International Journal of Oncology 42, no. 2 (2013): 651-656. https://doi.org/10.3892/ijo.2012.1753
Copy and paste a formatted citation
x
Spandidos Publications style
Lin J, Wei L, Shen A, Cai Q, Xu W, Li H, Zhan Y, Hong Z and Peng J: Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis. Int J Oncol 42: 651-656, 2013.
APA
Lin, J., Wei, L., Shen, A., Cai, Q., Xu, W., Li, H. ... Peng, J. (2013). Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis. International Journal of Oncology, 42, 651-656. https://doi.org/10.3892/ijo.2012.1753
MLA
Lin, J., Wei, L., Shen, A., Cai, Q., Xu, W., Li, H., Zhan, Y., Hong, Z., Peng, J."Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis". International Journal of Oncology 42.2 (2013): 651-656.
Chicago
Lin, J., Wei, L., Shen, A., Cai, Q., Xu, W., Li, H., Zhan, Y., Hong, Z., Peng, J."Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis". International Journal of Oncology 42, no. 2 (2013): 651-656. https://doi.org/10.3892/ijo.2012.1753
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