Download PDF
Planta Med 2010; 76(10): 956-962
DOI: 10.1055/s-0029-1240893
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Inhibition of Bone Metastasis from Breast Carcinoma by Rosmarinic Acid

Yichun Xu1 , Zijing Jiang1 , Guang Ji2 , Jianwen Liu1
  • 1State Key Laboratory of Bioreactor Engineering & School of Pharmacy, East China University of Science and Technology, Shanghai, P. R. China
  • 2Laboratory of Liver Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
Further Information

Publication History

received Dec. 1, 2009 revised January 1, 2010

accepted January 22, 2010

Publication Date:
15 February 2010 (online)

    Permissions and Reprints

Abstract

Skeletal disorders are a common complication of breast cancer and will be found in the vast majority of women with metastatic disease. Our study showed that rosmarinic acid (RA) could inhibit the migration of MDA‐MB-231BO human bone-homing breast cancer cells dose-dependently. Furthermore, in ST-2 murine bone marrow stromal cells cultured with RA there was a significant and dose-dependent increase in alkaline phosphatase (ALP) activity, with the number and size of mineralized nodules increasing. According to Western blot and quantitative real-time PCR assay, RA may inhibit bone metastasis from breast carcinoma mainly via the pathway of the receptor activator of NFκB ligand (RANKL)/RANK/osteoprotegerin (OPG) and by simultaneously suppressing the expression of interleukin-8 (IL-8). RA may thus be a good candidate for a new therapeutic approach in bone metastasis from breast carcinoma.

Key words

Prunella vulgaris L. - Lamiaceae - rosmarinic acid - bone metastasis - breast carcinoma

References

  • 1 Jemal A, Siegel R, Ward E. Cancer statistics.  CA Cancer J Clin. 2007;  57 43-66
    CrossrefPubMedGoogle Scholar
  • 2 Lipton A, Demers L, Daniloff Y. Increased urinary excretion of pyridinium crosslinks in cancer patients.  Clin Chem. 1993;  39 614-618
    PubMedGoogle Scholar
  • 3 Mundy G R. Metastasis to bone: causes, consequences and therapeutic opportunities.  Nat Rev Cancer. 2002;  2 584-593
    CrossrefPubMedGoogle Scholar
  • 4 Clines G A, Guise T A. Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone.  Endocr Relat Cancer. 2005;  12 549-583
    CrossrefPubMedGoogle Scholar
  • 5 Jemal A, Siegel R, Ward E. Cancer statistics.  CA Cancer J Clin. 2006;  56 106-130
    Google Scholar
  • 6 Body J J. Effectiveness and cost of bisphosphonate therapy in tumor bone disease.  Cancer. 2003;  97 859-865
    CrossrefPubMedGoogle Scholar
  • 7 Ma P L, Zhao P R, Tian A Q. The effect of Prunella vulgaris L. on Eca109 cells.  J Basic Clin Oncol. 2006;  19 199-200
    PubMedGoogle Scholar
  • 8 Qiao S, Li W, Subouchi R. Rosmarinic acid inhibits the formation of reactive oxygen and nitrogen species in RAW264.7 macrophages.  Free Radic Res. 2005;  39 995-1003
    CrossrefPubMedGoogle Scholar
  • 9 Youn J, Lee K H, Won J. Beneficial effects of rosmarinic acid on suppression of collagen induced arthritis.  J Rheumatol. 2003;  30 1203-1207
    PubMedGoogle Scholar
  • 10 Parnham M J, Kesselring K. Rosmarinic acid.  Drugs Future. 1985;  10 756-757
    PubMedGoogle Scholar
  • 11 Wang Z J, Zhao Y Y, Wang F. Depsides from Prunella vulgaris.  Chin Chem Lett. 2000;  11 997-1001
    PubMedGoogle Scholar
  • 12 Mareel M, Leroy A. Clinical, cellular, and molecular aspects of cancer invasion.  Physiol Rev. 2003;  83 337-376
    PubMedGoogle Scholar
  • 13 Hale L V, Ma Y F, Santerre R F. Semi-quantitative fluorescence analysis of calcein binding as a measurement of in vitro mineralization.  Calcif Tissue Int. 2000;  67 80-84
    CrossrefPubMedGoogle Scholar
  • 14 Zhang J, Shen Y L, Liu J W. Antimetastatic effect of RA through inhibition of tumor invasion.  Biochem Pharmacol. 2005;  69 407-414
    CrossrefPubMedGoogle Scholar
  • 15 Yoneda T, Hiraga T. Crosstalk between cancer cells and bone microenvironment in bone metastasis.  Biochem Biophys Res Commun. 2005;  328 679-687
    CrossrefPubMedGoogle Scholar
  • 16 Hofbauer L C, Neubauer A, Heufelder A E. Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: potential implications for the pathogenesis and treatment of malignant bone diseases.  Cancer. 2001;  92 460-470
    CrossrefPubMedGoogle Scholar
  • 17 Kong Y Y, Yoshida H, Sarosi I. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis.  Nature. 1999;  397 315-323
    CrossrefPubMedGoogle Scholar
  • 18 Hsu H, Lacey D L, Dunstan C R. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand.  Proc Natl Acad Sci USA. 1999;  96 3540-3545
    CrossrefPubMedGoogle Scholar
  • 19 Nakagawa N, Kinosaki M, Yamaguchi K. RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis.  Biochem Biophys Res Commun. 1998;  253 395-400
    CrossrefPubMedGoogle Scholar
  • 20 Lacey D L, Timms E, Tan H L. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.  Cell. 1998;  93 165-176
    CrossrefPubMedGoogle Scholar
  • 21 Morony S, Capparelli C, Sarosi I. Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis.  Cancer Res. 2001;  61 4432-4436
    PubMedGoogle Scholar
  • 22 Théoleyre S, Wittrant Y, Tat S K. The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling.  Cytokine Growth Factor Rev. 2004;  15 457-475
    CrossrefPubMedGoogle Scholar
  • 23 Lacey D L, Timms E, Tan H L. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.  Cell. 1998;  93 165-176
    CrossrefPubMedGoogle Scholar
  • 24 Simonet W S, Lacey D L, Dunstan C R. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.  Cell. 1997;  89 309-319
    CrossrefPubMedGoogle Scholar
  • 25 Williams G T, Smith C A, Spooncer E. Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis.  Nature. 1990;  343 76-79
    CrossrefPubMedGoogle Scholar
  • 26 Guise T A, Yin J J, Taylor S D. Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis.  J Clin Invest. 1996;  98 1544-1549
    CrossrefPubMedGoogle Scholar
  • 27 Chirgwin J M, Guise T A. Molecular mechanisms of tumor-bone interactions in osteolytic metastases.  Crit Rev Eukaryot Gene Expr. 2000;  10 159-178
    PubMedGoogle Scholar
  • 28 Chirgwin J M, Mohammad K S, Guise T A. Tumor-bone cellular interactions in skeletal metastases.  J Musculoskelet Neuronal Interact. 2004;  4 308-318
    PubMedGoogle Scholar
  • 29 Yoshimura T, Matsushima K, Tanaka S. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines.  Proc Natl Acad Sci USA. 1987;  84 9233-9237
    CrossrefPubMedGoogle Scholar
  • 30 Sozzani S, Locati M, Allavena P. Chemokines: a superfamily of chemotactic cytokines.  Int J Clin Lab Res. 1996;  26 69-82
    CrossrefPubMedGoogle Scholar
  • 31 Bendre M S, Gaddy-Kurten D, Mon-Foote T. Expression of interleukin-8 and not parathyroid hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo.  Cancer Res. 2002;  62 5571-5579
    PubMedGoogle Scholar
  • 32 Bendre M S, Margulies A G, Walser B. Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-κB ligand pathway.  Cancer Res. 2005;  65 11001-11009
    CrossrefPubMedGoogle Scholar
  • 33 Benoy I H, Salgado R, Van Dam P. Increased serum interleukin-8 in patients with early and metastatic breast cancer correlates with early dissemination and survival.  Clin Cancer Res. 2004;  10 7157-7162
    CrossrefPubMedGoogle Scholar
  • 34 Bendre M S, Montague D C, Peery T. Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease.  Bone. 2003;  33 28-37
    CrossrefPubMedGoogle Scholar
  • 35 Thudi N K, Martin C K, Nadella M V. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer.  Prostate. 2008;  68 1116-1125
    CrossrefPubMedGoogle Scholar

Guang Ji

Laboratory of Liver Disease
Longhua Hospital
Shanghai University of Traditional Chinese Medicine

No. 725 Wanping Road

Shanghai 200032

P. R. China

Phone: + 86 21 64 25 20 44

Fax: + 86 21 64 25 20 44

Email: jiliver@vip.sina.com

Jianwen Liu

State Key Laboratory of Bioreactor Engineering & School of Pharmacy
East China University of Science and Technology

No. 130 Meilong Road

Shanghai 200237

P. R. China

Phone: + 86 21 64 25 20 44

Fax: + 86 21 64 25 20 44

Email: liujian@ecust.edu.cn

    www.thieme-connect.de/ejournals/toc/plantamedica
>