Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
June-2014 Volume 44 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2014 Volume 44 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

In vitro and in vivo effects of a nutrient mixture on breast cancer progression

  • Authors:
    • M. W. Roomi
    • T. Kalinovsky
    • N. M. Roomi
    • J. Cha
    • M. Rath
    • A. Niedzwiecki
  • View Affiliations / Copyright

    Affiliations: Dr. Rath Research Institute, Santa Clara, CA 95050, USA
  • Pages: 1933-1944
    |
    Published online on: April 10, 2014
       https://doi.org/10.3892/ijo.2014.2379
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Long-term survival of patients with breast cancer remains poor, due to metastasis and recurrence. We investigated the effects of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract in vitro and in vivo on 4T1 murine breast cancer, a representative model for metastatic breast cancer. After one week of isolation, 5-6-week-old female Balb/C mice were inoculated with 5x105 4T1 cells into the mammary pad and randomly divided into two groups; the control group was fed a regular diet and the NM group a regular diet supplemented with 0.5% NM. After four weeks, the mice were sacrificed and their tumors, lungs, livers, kidneys, hearts and spleens were excised and processed for histology. Dimensions (length and width) of tumors were measured using a digital caliper, and the tumor burden was calculated using the following formula: 0.5 x length x width. We also tested the effect of NM in vitro on 4T1 cells, measuring cell proliferation by MTT assay, MMP secretion by zymography, invasion through Matrigel, migration by scratch test and morphology by H&E staining. NM inhibited tumor weight and burden of 4T1 tumors by 50% (p=0.02) and 53.4% (p≤0.0001), respectively. Lung metastasis was profoundly inhibited by NM supplementation: mean number of colonies was reduced by 87% (p<0.0001) and mean weight of lungs by 60% (p=0.0001) compared to control mice. Metastasis to liver, spleen, kidney and heart was significantly reduced with NM supplementation. In vitro, NM exhibited 50% toxicity over the control at 250 and 500 µg/ml concentrations. Zymography demonstrated MMP-2 and MMP-9 secretion which was inhibited by NM in a dose-dependent manner, with virtual total inhibition of both at 1,000 µg/ml. Migration by scratch test and invasion through Matrigel were inhibited in a dose-dependent manner with total block of invasion at 250 and of migration at 1,000 µg/ml. These results suggest that NM has therapeutic potential in the treatment of breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15

Figure 16

Figure 17

Figure 18

Figure 19

Figure 20

View References

1. 

American Cancer Society: Breast cancer: what are the key statistics about breast cancer? http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-key-statistics). Accessed 10/9/13. Last Medical Review: 09/11/2013. Last Revised: 10/01/2013.

2. 

Ali SM, Harvey HA and Lipton A: Metastatic breast cancer: overview of treatment. Clin Orthop. 414(Suppl): 132–137. 2003. View Article : Google Scholar

3. 

Fidler IJ: Molecular biology of cancer: invasion and metastasis. Cancer: Principles and Practice of Oncology. 5th edition. De Vita VT, Hellman S and Rosenberg SA: Lippincott-Raven; Philadelphia, PA: pp. 135–152. 1997

4. 

Rath M and Pauling L: Plasmin-induced proteolysis and the role of apoprotein(a), lysine and synthetic analogs. Orthomolecular Med. 7:17–23. 1992.

5. 

Niedzwiecki A, Roomi MW, Kalinovsky T and Rath M: Micronutrient synergy - a new tool in effective control of metastasis and other key mechanisms of cancer. Cancer Metastasis Rev. 29:529–543. 2010. View Article : Google Scholar : PubMed/NCBI

6. 

Bibby MC: Orthotopic models of cancer for preclinical drug evaluation: advantages and disadvantages. Eur J Cancer. 40:852–857. 2004. View Article : Google Scholar : PubMed/NCBI

7. 

Eccles SA, Box G, Court W, Sandle J and Dean CJ: Preclinical models for the evaluation of targeted therapies of metastatic disease. Cell Biophys. 24–25:279–291. 1994.

8. 

Hoffman RM: Orthotopic metastatic mouse models for anti-cancer drug discovery and evaluation: a bridge to the clinic. Invest New Drugs. 17:343–359. 1999. View Article : Google Scholar : PubMed/NCBI

9. 

Vernon E, Bakewell SJ and Chodash LA: Deciphering the molecular basis of breast cancer metastasis with mouse models. Rev Endocr Metab Disord. 8:199–213. 2007. View Article : Google Scholar : PubMed/NCBI

10. 

Tao K, Fang M, Aloy J and Sahagian GG: Imagable 4T1 model for the study of late stage breast cancer. BMC Cancer. 8:2282008. View Article : Google Scholar : PubMed/NCBI

11. 

Aslakson CJ and Miller FR: Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Res. 52:1399–1405. 1992.PubMed/NCBI

12. 

Bonfil RD, Bustuabad OD, Ruggiero RA, Meiss RP and Pasqualini CD: Tumor necrosis can facilitate the appearance of metastases. Clin Exp Metastasis. 6:121–129. 1988. View Article : Google Scholar : PubMed/NCBI

13. 

Bonfil RD, Medina PA, Gómez DE, Farías E, Lazarowski A, Lucero Gritti MF, Meiss RP and Bustuabad OD: Expression of gelatinase/type IV collagenase in tumor necrosis correlates with cell detachment and tumor invasion. Clin Exp Metastasis. 10:211–220. 1992. View Article : Google Scholar : PubMed/NCBI

14. 

Cha J, Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A and Rath M: Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C deficient mice. Int J Oncol. 42:55–64. 2013.PubMed/NCBI

15. 

Bachmeier BE, Nerlich AG, Lichtinghagen R and Sommerhoff CP: Matrix metalloproteinases (MMPs) in breast cancer cell lines of different tumorigenicity. Anticancer Res. 6A:3821–3828. 2001.PubMed/NCBI

16. 

Pellikainen JM, Ropponen KM, Kataja VV, Kellokoski JK, Eskelinen MJ and Kosma VM: Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER-2, and prognosis. Clin Cancer Res. 10:7621–7628. 2004. View Article : Google Scholar : PubMed/NCBI

17. 

Connolly EM, Harmey JH, O'Grady T, Foley D, Roche-Nagle G, Kay E and Bouchier-Hayes DJ: Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer. Br J Cancer. 87:231–237. 2002. View Article : Google Scholar : PubMed/NCBI

18. 

Denardo DG, Johansson M and Coussans LM: Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev. 27:11–18. 2008. View Article : Google Scholar : PubMed/NCBI

19. 

van Kempen LC, de Visser KE and Coussens LM: Inflammation, proteases and cancer. Eur J Cancer. 42:728–734. 2006.PubMed/NCBI

20. 

Roomi MW, Kalinovsky T, Roomi NW, Rath M and Niedzwiecki A: Inhibition of growth and expression of inflammation mediators in human leukemic cell line. Exp Oncol. 35:180–186. 2013.PubMed/NCBI

21. 

Roomi MW, Kalinovsky T, Niedzwiecki A and Rath M: Pleiotropic effects of a micronutrient mixture on critical parameters of bladder cancer. Bladder Cancer Etymology, Diagnosis and Treatments. Nilsson WE: Nova Science Publishers, Inc.; New York: 2009

22. 

Sun Z, Chen YH, Wang P, Zhang J, Gurewich V, Zhang P and Liu JN: The blockage of high-affinity lysine binding sites of plasminogen by EACA significantly inhibits prourokinase-induced plasminogen activation. Biochem Biophys Acta. 1596:182–192. 2002.PubMed/NCBI

23. 

Valcic S, Timmermann BN, Alberts DS, Wachter GA, Krutzsch M, Wymer J and Guillen JM: Inhibitory effect of six green tea catechins and caffeine on the growth of four selected human tumor cell lines. Anticancer Drugs. 7:461–468. 1996. View Article : Google Scholar : PubMed/NCBI

24. 

Mukhtar H and Ahmed N: Tea polyphenols: prevention of cancer and optimizing health. Am J Clin Nutr. 71:S1698–S1702. 2000.PubMed/NCBI

25. 

Yang GY, Liao J, Kim K, Yurtow EJ and Yang CS: Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis. 19:611–616. 1998. View Article : Google Scholar : PubMed/NCBI

26. 

Taniguchi S, Fujiki H, Kobayashi H, Go H, Miyado K, Sadano H and Shimikawa R: Effect of (−) epigallocatechin gallate, the main constituent of green tea, on lung metastasis with mouse B16 melanoma cell lines. Cancer Lett. 65:51–54. 1992.

27. 

Hara Y: Green tea: Health Benefits and Applications. Marcel Dekker; New York, Basel: 2001, View Article : Google Scholar

28. 

Kawakami S, Kageyama Y, Fujii Y, Kihara K and Oshima H: Inhibitory effects of N-acetyl cysteine on invasion and MMP 9 production of T24 human bladder cancer cells. Anticancer Res. 21:213–219. 2001.PubMed/NCBI

29. 

Morini M, Cai T, Aluigi MG, Noonan DM, Masiello L, De Floro S, D’Agostinin F, Albini A and Fassima G: The role of the thiol N-acetyl cysteine in the prevention of tumor invasion and angiogenesis. Int J Biol Markers. 14:268–271. 1999.PubMed/NCBI

30. 

Yoon SO, Kim MM and Chung AS: Inhibitory effects of selenite on invasion of HT 1080 tumor cells. J Biol Chem. 276:20085–20092. 2001. View Article : Google Scholar : PubMed/NCBI

31. 

Naidu KA, Karl RC and Coppola D: Antiproliferative and proapoptotic effect of ascorbyl stearate in human pancreatic cancer cells: association with decreased expression of insulin-like growth factor 1 receptor. Dig Dis Sci. 48:230–237. 2003. View Article : Google Scholar : PubMed/NCBI

32. 

Anthony HM and Schorah CJ: Severe hypovitaminosis C in lung-cancer patients: the utilization of vitamin C in surgical repair and lymphocyte-related host resistance. Br J Cancer. 46:354–367. 1982. View Article : Google Scholar : PubMed/NCBI

33. 

Maramag C, Menon M, Balaji KC, Reddy PG and Laxmanan S: Effect of vitamin C on prostate cancer cells in vitro: effect on cell number, viability and DNA synthesis. Prostate. 32:188–195. 1997. View Article : Google Scholar : PubMed/NCBI

34. 

Koh WS, Lee SJ, Lee H, Park C, Park MH, Kim WS, Yoon SS, Park K, Hong SI, Chung MH and Park CH: Differential effects and transport kinetics of ascorbate derivatives in leukemic cell lines. Anticancer Res. 8:2487–2493. 1998.PubMed/NCBI

35. 

Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E and Levine M: Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA. 102:13604–13609. 2005. View Article : Google Scholar : PubMed/NCBI

36. 

Nunez C, Ortiz de Apodaca Y and Ruiz A: Ascorbic acid in the plasma and blood cells of women with breast cancer. The effect of consumption of food with an elevated content of this vitamin. Nutr Hosp. 10:368–372. 1995.PubMed/NCBI

37. 

Kurbacher CM, Wagner U, Kolster B, Andreotti PE, Krebs D and Bruckner HW: Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett. 103:183–189. 1996. View Article : Google Scholar : PubMed/NCBI

38. 

Cooke JP and Dzau VJ: Nitric oxide synthase: role in the genesis of vascular disease. Annu Rev Med. 48:489–509. 1997. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Roomi MW, Kalinovsky T, Roomi NM, Cha J, Rath M and Niedzwiecki A: In vitro and in vivo effects of a nutrient mixture on breast cancer progression. Int J Oncol 44: 1933-1944, 2014.
APA
Roomi, M.W., Kalinovsky, T., Roomi, N.M., Cha, J., Rath, M., & Niedzwiecki, A. (2014). In vitro and in vivo effects of a nutrient mixture on breast cancer progression. International Journal of Oncology, 44, 1933-1944. https://doi.org/10.3892/ijo.2014.2379
MLA
Roomi, M. W., Kalinovsky, T., Roomi, N. M., Cha, J., Rath, M., Niedzwiecki, A."In vitro and in vivo effects of a nutrient mixture on breast cancer progression". International Journal of Oncology 44.6 (2014): 1933-1944.
Chicago
Roomi, M. W., Kalinovsky, T., Roomi, N. M., Cha, J., Rath, M., Niedzwiecki, A."In vitro and in vivo effects of a nutrient mixture on breast cancer progression". International Journal of Oncology 44, no. 6 (2014): 1933-1944. https://doi.org/10.3892/ijo.2014.2379
Copy and paste a formatted citation
x
Spandidos Publications style
Roomi MW, Kalinovsky T, Roomi NM, Cha J, Rath M and Niedzwiecki A: In vitro and in vivo effects of a nutrient mixture on breast cancer progression. Int J Oncol 44: 1933-1944, 2014.
APA
Roomi, M.W., Kalinovsky, T., Roomi, N.M., Cha, J., Rath, M., & Niedzwiecki, A. (2014). In vitro and in vivo effects of a nutrient mixture on breast cancer progression. International Journal of Oncology, 44, 1933-1944. https://doi.org/10.3892/ijo.2014.2379
MLA
Roomi, M. W., Kalinovsky, T., Roomi, N. M., Cha, J., Rath, M., Niedzwiecki, A."In vitro and in vivo effects of a nutrient mixture on breast cancer progression". International Journal of Oncology 44.6 (2014): 1933-1944.
Chicago
Roomi, M. W., Kalinovsky, T., Roomi, N. M., Cha, J., Rath, M., Niedzwiecki, A."In vitro and in vivo effects of a nutrient mixture on breast cancer progression". International Journal of Oncology 44, no. 6 (2014): 1933-1944. https://doi.org/10.3892/ijo.2014.2379
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team