Skip to main content

Advertisement

SpringerLink
Log in

Diet modulation is an effective complementary agent in preventing and treating breast cancer lung metastasis

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

A significant percentage of breast cancer victims will suffer from metastases indicating that new approaches to preventing breast cancer metastasis are thus needed. Dietary stearate (ST) and chemotherapy have been shown to reduce breast cancer metastasis. We tested the complementary use of dietary ST with a taxol-based chemotherapy which work through separate mechanisms to reduce breast cancer metastasis. We therefore carried out a prevention study in which diets were initiated prior to human MDA-MB-435 cancer cells being injected into the host and a treatment study in which diets were combined with paclitaxel (PTX). Using an orthotopic athymic nude mouse model and three diets [corn oil (CO) control diet, low fat (LF) or ST] the prevention study demonstrated that the ST diet decreased the incidence of lung metastasis by 50 % compared to both the LF and CO diets. The ST diet also reduced the number and size of metastatic lung nodules compared to the LF diet. Results of the treatment study indicated that both the CO and ST diets decreased the number of mice with lung metastasis compared to the LF diet. Both CO and ST also decreased the number of lung metastases per mouse compared to the LF diet however only the ST diet cohort was significant. Histomorphometric analysis of the lung tumor tissue indicated that the ST diet plus PTX decreased angiogenesis compared to the LF diet plus PTX. In conclusion these results support combining diet with chemotherapy in both treatment and prevention settings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

LF:

Low fat diet

CO:

Corn oil diet

ST:

Stearate diet

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. Saloustros E, Mavroudis D, Georgoulias V (2008) Paclitaxel and docetaxel in the treatment of breast cancer. Expert Opin Pharmacother 9:2603–2616

    Article  CAS  PubMed  Google Scholar 

  3. Pienta K (2001) Preclinical mechanisms of action of docetaxel and docetaxel combinations in prostate cancer. Semin Oncol 28(4 Suppl 15):3–7

    Article  CAS  PubMed  Google Scholar 

  4. Bogenrieder T, Herlyn M (2003) Axis of evil: molecular mechanisms of cancer metastasis. Oncogene 22:6524–6536

    Article  CAS  PubMed  Google Scholar 

  5. Greenlee RT, Hill-Harmon MB, Murray T, Thun M (2001) Cancer statistics, 2001. CA Cancer J Clin 51:15–36

    Article  CAS  PubMed  Google Scholar 

  6. Chung CT, Carlson RW (2003) Goals and objectives in the management of metastatic breast cancer. Oncologist 8:514–520

    Article  PubMed  Google Scholar 

  7. Grundy SM (1994) Influence of stearic acid on cholesterol metabolism relative to other long-chain fatty acids. Am J Clin Nutr 60:986S–990S

    CAS  PubMed  Google Scholar 

  8. Hunter JE, Zhang J, Kris-Etherton PM (2010) Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review. Am J Clin Nutr 91:46–63

    Article  CAS  PubMed  Google Scholar 

  9. Tinsley IJ, Schmitz JA, Pierce DA (1981) Influence of dietary fatty acids on the incidence of mammary tumors in the C3H mouse. Cancer Res 41:1460–1465

    CAS  PubMed  Google Scholar 

  10. Bennett AS (1984) Effect of dietary stearic acid on the genesis of spontaneous mammary adenocarcinomas in strain A/ST mice. Int J Cancer 34:529–533

    CAS  PubMed  Google Scholar 

  11. Habib NA, Wood CB, Apostolov K, Barker W, Hershman MJ, Aslam M, Heinemann D, Fermor B, Williamson RC, Jenkins WE et al (1987) Stearic acid and carcinogenesis. Br J Cancer 56:455–458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Singh RK, Hardy RW, Wang MH, Williford J, Gladson CL, McDonald JM, Siegal GP (1995) Stearate inhibits human tumor cell invasion. Invasion Metastasis 15:144–155

    CAS  PubMed  Google Scholar 

  13. Wickramasinghe NS, Jo H, McDonald JM, Hardy RW (1996) Stearate inhibition of breast cancer cell proliferation. A mechanism involving epidermal growth factor receptor and G-proteins. Am J Pathol 148:987–995

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Hardy S, El-Assaad W, Przybytkowski E, Joly E, Prentki M, Langelier Y (2003) Saturated fatty acid-induced apoptosis in MDA-MB-231 breast cancer cells. A role for cardiolipin. J Biol Chem 278:31861–31870

    Article  CAS  PubMed  Google Scholar 

  15. Evans LM, Cowey SL, Siegal GP, Hardy RW (2009) Stearate preferentially induces apoptosis in human breast cancer cells. Nutr Cancer 61:746–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Evans LM, Toline EC, Desmond R, Siegal GP, Hashim AI, Hardy RW (2009) Dietary stearate reduces human breast cancer metastasis burden in athymic nude mice. Clin Exp Metastasis 26:415–424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li C, Zhao X, Toline E, Siegal GP, Evans LM, Ibrahim-Hashim A, Desmond R, Hardy RW (2011) Prevention of carcinogenesis and inhibition of breast cancer tumor burden by dietary stearate. Carcinogenesis 32:1251–1258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Townson JL, Naumov GN, Chambers AF (2003) The role of apoptosis in tumor progression and metastasis. Curr Mol Med 3:631–642

    Article  CAS  PubMed  Google Scholar 

  19. Boedefeld WM II, Bland KI, Heslin MJ (2003) Recent insights into angiogenesis, apoptosis, invasion, and metastasis in colorectal carcinoma. Ann Surg Oncol 10:839–851

    Article  PubMed  Google Scholar 

  20. Weidner N (1995) Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 36:169–180

    Article  CAS  PubMed  Google Scholar 

  21. Ingber DE (2008) Can cancer be reversed by engineering the tumor micro-environment? Semin Cancer Biol 18:356–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schmitz AA, Govek EE, Böttner B, Van Aelst L (2000) Rho GTPases: signaling, migration, and invasion. Exp Cell Res 25:1–12

    Article  Google Scholar 

  23. Merajver SD, Usmani SZ (2005) Multifaceted role of Rho proteins in angiogenesis. J Mammary Gland Biol Neoplasia 10:291–298

    Article  PubMed  Google Scholar 

  24. Pillé JY, Denoyelle C, Varet J et al (2005) Anti-RhoA and anti-RhoC siRNAs inhibit the proliferation and invasiveness of MDA-MB-231 breast cancer cells in vitro and in vivo. Mol Ther 11:267–274

    Article  PubMed  Google Scholar 

  25. Welsch CW (1992) Dietary fat, calories, and mammary gland tumorigenesis. Adv Exp Med Biol 322:203–222

    Article  CAS  PubMed  Google Scholar 

  26. Rose DP, Connolly JM (1992) Influence of dietary fat intake on local recurrence and progression of metastases arising from MDA-MB-435 human breast cancer cells in nude mice after excision of the primary tumor. Nutr Cancer 18:113–122

    Article  CAS  PubMed  Google Scholar 

  27. Warburg O, Wind F, Negelein E (1927) The metabolism of tumors in the body. J Gen Physiol 8:519–530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Klement RJ, Kammerer U (2011) Is there a role for carbohydrate restriction in the treatment and prevention of cancer? Nutr Metab 8:75

    Article  CAS  Google Scholar 

  29. Saadatian-Elahi M, Norat T, Goudable J, Riboli E (2004) Biomarkers of dietary fatty acid intake and the risk of breast cancer: a meta-analysis. Int J Cancer 111:584–591

    CAS  PubMed  Google Scholar 

  30. Munaron L (2006) Intracellular calcium, endothelial cells and angiogenesis. Recent Pat Anticancer Drug Discov 1:105–119

    Article  CAS  PubMed  Google Scholar 

  31. Naumova E, Ubezio P, Garofalo A et al (2006) The vascular targeting property of paclitaxel is enhanced by SU6668, a receptor tyrosine kinase inhibitor, causing apoptosis of endothelial cells and inhibition of angiogenesis. Clin Cancer Res 12:1839–1849

    Article  CAS  PubMed  Google Scholar 

  32. Dong LF, Swettenham E, Eliasson J et al (2007) Vitamin E analogues inhibit angiogenesis by selective induction of apoptosis in proliferating endothelial cells: the role of oxidative stress. Cancer Res 67:11906–11913

    Article  CAS  PubMed  Google Scholar 

  33. Artwohl M, Roden M, Waldhäusl W et al (2004) Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells. FASEB J 18:146–158

    CAS  PubMed  Google Scholar 

  34. Artwohl M, Lindenmair A, Sexl V et al (2008) Different mechanisms of saturated versus polyunsaturated FFA-induced apoptosis in human endothelial cells. J Lipid Res 49:2627–2640

    Article  CAS  PubMed  Google Scholar 

  35. Chambers AF (2009) MDA-MB-435 and M14 cell lines: identical but not M14 melanoma? Cancer Res 69:5292–5293

    Article  CAS  PubMed  Google Scholar 

  36. Nerlich AG, Bachmeier BE (2013) Density-dependent lineage instability of MDA-MB-435 breast cancer cells. Oncol Lett 5:1370–1374

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Rae JM, Creighton CJ, Meck JM et al (2007) MDA-MB-435 cells are derived from M14 melanoma cells: a loss for breast cancer, but a boon for melanoma research. Breast Cancer Res Treat 104:13–19

    Article  PubMed  Google Scholar 

  38. Christgen M, Lehmann U (2007) MDA-MB-435: the questionable use of a melanoma cell line as a model for human breast cancer is ongoing. Cancer Biol Ther 6:1355–1357

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by the UAB SPORE in Breast Cancer 5P50CA089019. We express our appreciation to the UAB Metabolic Bone Disease Histomorphometry Core Laboratory for processing the formalin-fixed paraffin-embedded sections, and carrying out the immunostaining and histomorphometry.

Author information

Authors and Affiliations

  1. Department of Pathology, University of Alabama at Birmingham, 701 South 19th Street, LHRB Room 531, Birmingham, AL, 35294, USA

    Xiangmin Zhao, Gabriel Rezonzew, Dezhi Wang, Gene P. Siegal & Robert W. Hardy

  2. Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, 35233, USA

    Dezhi Wang & Gene P. Siegal

  3. Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA

    Gene P. Siegal

  4. The UAB Center for Metabolic Bone Disease, Birmingham, AL, 35233, USA

    Gene P. Siegal & Robert W. Hardy

  5. The UAB Comprehensive Cancer Center, Birmingham, AL, 35233, USA

    Dezhi Wang, Gene P. Siegal & Robert W. Hardy

Authors
  1. Xiangmin Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriel Rezonzew
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dezhi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gene P. Siegal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert W. Hardy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert W. Hardy.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 192 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, X., Rezonzew, G., Wang, D. et al. Diet modulation is an effective complementary agent in preventing and treating breast cancer lung metastasis. Clin Exp Metastasis 31, 625–638 (2014). https://doi.org/10.1007/s10585-014-9654-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-014-9654-5

Keywords

Search

Navigation