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Beta-elemene inhibits melanoma growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis

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Abstract

Purpose

It was to assess antiangiogenic effect of β-elemene in vitro and in vivo, and it was involved in inhibiting melanoma growth and metastasis, as well as to elucidate its intrinsic mechanism.

Methods

Inhibitive effect of β-elemene on B16F10 cells was performed by cell proliferation assay. Angiogenesis assays in vitro including rat aortic ring and chick embryo chorioallantoic membrane were used, as well as melanoma growth and metastasis assay in C57BL/6 mice. Vascular endothelial growth factor (VEGF) expression in vitro and in vivo was measured respectively by western blot analysis and enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry analysis of CD34 and VEGF expression in primary melanoma was also presented.

Results

β-Elemene inhibited B16BF10 cell proliferation starting from 200 μM, but VEGF from 20 μM. Both 20 and 50 μM β-elemene in vitro inhibited VEGF-induced sprouting vessel of rat aortic ring and microvessel formation of chick embryo chorioallantoic membrane. In vivo, tumor size of primary melanoma in mice intraperitoneally treated with β-elemene was significantly smaller than that of the control; CD34 expression of primary melanoma was also suppressed; and the metastatic melanoma colonies and content of melanin in lung were detected obviously decreased in mice of β-elemene-treated groups. Furthermore, results of VEGF expressing in primary melanoma, serum and lung of mice also disclosed that VEGF was inhibited in vivo.

Conclusions

β-Elemene inhibited melanoma growth and metastasis through suppressing VEGF-mediated angiogenesis. It is a natural potential antiangiogenic agent.

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References

  1. Jerant AF, Johnson JT, Sheridan CD, Caffrey TJ (2000) Early detection and treatment of skin cancer. Am Fam Physician 62:357–368 375–356, 381–352

    PubMed  CAS  Google Scholar 

  2. Jahng AW, Liao SS (2006) Successful palliation with octreotide of a neuroendocrine syndrome from malignant melanoma. J Pain Symptom Manage 32:191–195

    Article  PubMed  Google Scholar 

  3. Guadagnolo BA, Zagars GK (2009) Adjuvant radiation therapy for high-risk nodal metastases from cutaneous melanoma. Lancet Oncol 10:409–416

    Article  PubMed  Google Scholar 

  4. Lorigan P, Eisen T, Hauschild A (2008) Systemic therapy for metastatic malignant melanoma–from deeply disappointing to bright future? Exp Dermatol 17:383–394

    Article  PubMed  CAS  Google Scholar 

  5. Berk LB (2008) Radiation therapy as primary and adjuvant treatment for local and regional melanoma. Cancer Control 15:233–238

    PubMed  Google Scholar 

  6. Tuma RS (2008) Mechanisms of metastasis: theories focus on microenvironment, host factors, genes. J Natl Cancer Inst 100:1752–1754

    Article  PubMed  Google Scholar 

  7. Mehlen P, Puisieux A (2006) Metastasis: a question of life or death. Nat Rev Cancer 6:449–458

    Article  PubMed  CAS  Google Scholar 

  8. Nguyen DX, Bos PD, Massague J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9:274–284

    Article  PubMed  CAS  Google Scholar 

  9. Kerbel RS (2008) Tumor angiogenesis. N Engl J Med 358:2039–2049

    Article  PubMed  CAS  Google Scholar 

  10. Streit M, Detmar M (2003) Angiogenesis, lymphangiogenesis, and melanoma metastasis. Oncogene 22:3172–3179

    Article  PubMed  CAS  Google Scholar 

  11. van Hinsbergh VW, Collen A, Koolwijk P (2001) Role of fibrin matrix in angiogenesis. Ann NY Acad Sci 936:426–437

    Article  PubMed  Google Scholar 

  12. Zetter BR (1998) Angiogenesis and tumor metastasis. Annu Rev Med 49:407–424

    Article  PubMed  CAS  Google Scholar 

  13. Lai EY, Chyau CC, Mau JL, Chen CC, Lai YJ (2004) Antimicrobial activity and cytotoxicity of the essential oil of Curcuma zedoaria. Am J Chin Med 32:281–290

    Article  PubMed  CAS  Google Scholar 

  14. Zhu R, Yang L, Shen L, Ye J, Liu J (2009) ANG II-AT1 receptor pathway is involved in the anti-fibrotic effect of beta-elemene. J Huazhong Univ Sci Technol Med Sci 29:177–181

    Article  PubMed  Google Scholar 

  15. Wang G, Li X, Huang F, Zhao J, Ding H (2005) Antitumor effect of beta-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death. Cell Mol Life Sci 62:881–893

    Article  PubMed  CAS  Google Scholar 

  16. Yao YQ, Ding X, Jia YC, Huang CX, Wang YZ (2008) Anti-tumor effect of beta-elemene in glioblastoma cells depends on p38 MAPK activation. Cancer Lett 264:127–134

    Article  PubMed  CAS  Google Scholar 

  17. Nicosia RF, Ottinetti A (1990) Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro. Lab Invest 63:115–122

    PubMed  CAS  Google Scholar 

  18. Brooks PC, Montgomery AM, Cheresh DA (1999) Use of the 10-day-old chick embryo model for studying angiogenesis. Methods Mol Biol 129:257–269

    PubMed  CAS  Google Scholar 

  19. Ito A, Morita N, Miura D, Koma Y, Kataoka TR (2004) A derivative of oleamide potently inhibits the spontaneous metastasis of mouse melanoma BL6 cells. Carcinogenesis 25:2015–2022

    Article  PubMed  CAS  Google Scholar 

  20. Boehm T, Folkman J, Browder T, O’Reilly MS (1997) Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390:404–407

    Article  PubMed  CAS  Google Scholar 

  21. Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med 324:1–8

    Article  PubMed  CAS  Google Scholar 

  22. Watts KP, Fairchild RG, Slatkin DN, Greenberg D, Packer S (1981) Melanin content of hamster tissues, human tissues, and various melanomas. Cancer Res 41:467–472

    PubMed  CAS  Google Scholar 

  23. Li X, Wang G, Zhao J, Ding H, Cunningham C (2005) Antiproliferative effect of beta-elemene in chemoresistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-M phase. Cell Mol Life Sci 62:894–904

    Article  PubMed  CAS  Google Scholar 

  24. Khosravi Shahi P, Fernandez Pineda I (2008) Tumoral angiogenesis: review of the literature. Cancer Invest 26:104–108

    Article  PubMed  Google Scholar 

  25. Stackpole CW, Alterman AL, Valle EF (1991) B16 melanoma variants selected by one or more cycles of spontaneous metastasis to the same organ fail to exhibit organ specificity. Clin Exp Metastasis 9:319–332

    Article  PubMed  CAS  Google Scholar 

  26. Panteli K, Zagorianakou N, Bai M, Katsaraki A, Agnantis NJ (2004) Angiogenesis in chronic myeloproliferative diseases detected by CD34 expression. Eur J Haematol 72:410–415

    Article  PubMed  CAS  Google Scholar 

  27. Vieira SC, Silva BB, Pinto GA, Vassallo J, Moraes NG (2005) CD34 as a marker for evaluating angiogenesis in cervical cancer. Pathol Res Pract 201:313–318

    Article  PubMed  CAS  Google Scholar 

  28. Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82:4–6

    Article  PubMed  CAS  Google Scholar 

  29. Sridhar SS, Shepherd FA (2003) Targeting angiogenesis: a review of angiogenesis inhibitors in the treatment of lung cancer. Lung Cancer 42(Suppl 1):S81–S91

    Article  PubMed  Google Scholar 

  30. Kerr DJ (2004) Targeting angiogenesis in cancer: clinical development of bevacizumab. Nat Clin Pract Oncol 1:39–43

    Article  PubMed  CAS  Google Scholar 

  31. Stein MN, Flaherty KT (2007) CCR drug updates: sorafenib and sunitinib in renal cell carcinoma. Clin Cancer Res 13:3765–3770

    Article  PubMed  CAS  Google Scholar 

  32. Wang Y, Fang MY, Jiang F, Peng HJ (2004) Effects of arsenic trioxide, ginseng saponin and beta-elemene on telomere-telomerase system in K562 cell line. Zhongguo Shi Yan Xue Ye Xue Za Zhi 12:315–320

    PubMed  CAS  Google Scholar 

  33. Xu YH, Dong B, Luo QZ, Zhou HY, Jia YC (2005) Influence of elemene on the expression of Bcl-2 family genes in rat C6 glioma cells. Zhonghua Yi Xue Za Zhi 85:1700–1703

    PubMed  CAS  Google Scholar 

  34. Losordo DW, Isner JM (2001) Estrogen and angiogenesis: a review. Arterioscler Thromb Vasc Biol 21:6–12

    PubMed  CAS  Google Scholar 

  35. Xue Q, Nagy JA, Manseau EJ, Phung TL, Dvorak HF, Benjamin LE (2009) Rapamycin inhibition of the Akt/mTOR pathway blocks select stages of VEGF-A164-driven angiogenesis, in part by blocking S6Kinase. Arterioscler Thromb Vasc Biol 29:1172–1178

    Article  PubMed  CAS  Google Scholar 

  36. Kitamura T, Asai N, Enomoto A, Maeda K, Kato T, Ishida M, Jiang P, Watanabe T, Usukura J, Kondo T, Costantini F, Murohara T, Takahashi M (2008) Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin. Nat Cell Biol 10:329–337

    Article  PubMed  CAS  Google Scholar 

  37. Matsumoto T, Claesson-Welsh L (2001) VEGF receptor signal transduction. Sci STKE 112:re21

    Google Scholar 

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Acknowledgments

This work was supported by National Natural Science Foundation of China (30801545), Jiangsu Administration of Chinese Medicine Foundation (HZ07052) and Nanjing University of Chinese Medicine Foundation (07XZR08).

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Authors and Affiliations

  1. College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Highway, 210046, Nanjing, China

    Wenxing Chen, Yin Lu, Jiaming Wu, Ming Gao, Aiyun Wang & Bo Xu

  2. Jiangsu Key Laboratory for Traditional Chinese Medicine Formulae Research, Nanjing University of Chinese Medicine, 138 Xianlin Highway, 210046, Nanjing, China

    Wenxing Chen, Yin Lu & Aiyun Wang

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  1. Wenxing Chen
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  2. Yin Lu
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  3. Jiaming Wu
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Correspondence to Wenxing Chen.

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Chen, W., Lu, Y., Wu, J. et al. Beta-elemene inhibits melanoma growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis. Cancer Chemother Pharmacol 67, 799–808 (2011). https://doi.org/10.1007/s00280-010-1378-x

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  • DOI: https://doi.org/10.1007/s00280-010-1378-x

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