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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
March-2016 Volume 11 Issue 3

Full Size Image

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
March-2016 Volume 11 Issue 3

Full Size Image

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

Combination of lactate calcium salt with 5‑indanesulfonamide and α‑cyano‑4‑hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification

  • Authors:
    • Keun‑Yeong Jeong
    • Poonam Mander
    • Jae Jun Sim
    • Hwan Mook Kim
  • View Affiliations / Copyright

    Affiliations: College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 406‑840, Republic of Korea
  • Pages: 1866-1872
    |
    Published online on: January 20, 2016
       https://doi.org/10.3892/ol.2016.4137
  • 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

Maintenance of a neutral intracellular pH (pHi) is favorable for the survival of tumors, and maintenance of highly acidic extracellular pH (pHe) facilitates tumor invasiveness. The aim of the present study was to investigate the antitumor effects of lactate calcium salt (CaLa), 5‑indanesulfonamide (IS) and α‑cyano‑4‑hydroxycinnamic acid (CA) via pH regulation in colon cancer cells. HCT116 cells were treated with CaLa, IS, CA and combinations of the three. Subsequently, the concentration of intracellular lactate was determined. pHi and pHe were measured using cell lysates and culture media. Colony formation assay, cell viability assay and western blot analysis were additionally performed to analyze the consequences of the pH changes. CaLa, IS, CA and combination treatments induced an increase in the concentration of intracellular lactate. Lactate influx into the tumor microenvironment produced an acidic pHi in colon cancer cells. Consequently, colony formation and cell viability were significantly decreased, as well as poly(adenosine diphosphate‑ribose) polymerase degradation. The tumor microenvironment may be exploited therapeutically by disrupting the mechanism that regulates pHi, leading to cell apoptosis. The present study indicated that treatment with CaLa, IS and CA induced intracellular acidification via lactate influx, causing apoptosis of colon cancer cells. Additionally, the findings suggested that the combination of CaLa with IS and CA may enhance antitumor activity, and may provide a potential therapeutic approach for the treatment of colon cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Benito M and Díaz-Rubio E: Molecular biology in colorectal cancer. Clin Transl Oncol. 8:391–398. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Parks SK, Chiche J and Pouyssegur J: pH control mechanisms of tumor survival and growth. J Cell Physiol. 226:299–308. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Swietach P, Patiar S, Supuran CT, Harris AL and Vaughan-Jones RD: The role of carbonic anhydrase 9 in regulating extracellular and intracellular pH in three-dimensional tumor cell growths. J Biol Chem. 284:20299–20310. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Doherty JR and Cleveland JL: Targeting lactate metabolism for cancer therapeutics. J Clin Invest. 123:3685–3692. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Semenza GL: Tumor metabolism: Cancer cells give and take lactate. J Clin Invest. 118:3835–3837. 2008.PubMed/NCBI

7 

Kato Y, Ozawa S, Miyamoto C, Maehata Y, Suzuki A, Maeda T and Baba Y: Acidic extracellular microenvironment and cancer. Cancer Cell Int. 13:892013. View Article : Google Scholar : PubMed/NCBI

8 

Swietach P, Vaughan-Jones RD and Harris AL: Regulation of tumor pH and the role of carbonic anhydrase 9. Cancer Metastasis Rev. 26:299–310. 2007. View Article : Google Scholar : PubMed/NCBI

9 

McDonald PC, Winum JY, Supuran CT and Dedhar S: Recent developments in targeting carbonic anhydrase IX for cancer therapeutics. Oncotarget. 3:84–97. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Gu MJ and Kwon KW: Carbonic anhydrase IX expression is associated with favorable prognostic factors in small intestinal carcinoma. J Histochem Cytochem. 62:205–210. 2014. View Article : Google Scholar : PubMed/NCBI

11 

McIntyre A, Patiar S, Wigfield S, Li JL, Ledaki I, Turley H, Leek R, Snell C, Gatter K, Sly WS, et al: Carbonic anhydrase IX promotes tumor growth and necrosis in vivo and inhibition enhances anti-VEGF therapy. Clin Cancer Res. 18:3100–3111. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Dubois L, Peeters S, Lieuwes NG, Geusens N, Thiry A, Wigfield S, Carta F, McIntyre A, Scozzafava A, Dogné JM, et al: Specific inhibition of carbonic anhydrase IX activity enhances the in vivo therapeutic effect of tumor irradiation. Radiother Oncol. 99:424–431. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Chiche J, Ilc K, Laferrière J, Trottier E, Dayan F, Mazure NM, Brahimi-Horn MC and Pouysségur J: Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH. Cancer Res. 69:358–368. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Nguyen TT and Bonanno JA: Bicarbonate, NBCe1, NHE, and carbonic anhydrase activity enhance lactate-H+ transport in bovine corneal endothelium. Invest Ophthalmol Vis Sci. 52:8086–8093. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Nakayama Y, Torigoe T, Inoue Y, Minagawa N, Izumi H, Kohno K and Yamaguchi K: Prognostic significance of monocarboxylate transporter 4 expression in patients with colorectal cancer. Exp Ther Med. 3:25–30. 2012.PubMed/NCBI

16 

Dimmer KS, Friedrich B, Lang F, Deitmer JW and Bröer S: The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochem J. 350:219–227. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Gotanda Y, Akagi Y, Kawahara A, Kinugasa T, Yoshida T, Ryu Y, Shiratsuchi I, Kage M and Shirouzu K: Expression of monocarboxylate transporter (MCT)-4 in colorectal cancer and its role: MCT4 contributes to the growth of colorectal cancer with vascular endothelial growth factor. Anticancer Res. 33:2941–2947. 2013.PubMed/NCBI

18 

Hussien R and Brooks GA: Mitochondrial and plasma membrane lactate transporter and lactate dehydrogenase isoform expression in breast cancer cell lines. Physiol Genomics. 43:255–264. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Lou Y, McDonald PC, Oloumi A, Chia S, Ostlund C, Ahmadi A, Kyle A, dem Keller Auf U, Leung S, Huntsman D, et al: Targeting tumor hypoxia: Suppression of breast tumor growth and metastasis by novel carbonic anhydrase IX inhibitors. Cancer Res. 71:3364–3376. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Pacchiano F, Carta F, McDonald PC, Lou Y, Vullo D, Scozzafava A, Dedhar S and Supuran CT: Ureido-substituted benzenesulfonamides potently inhibit carbonic anhydrase IX and show antimetastatic activity in a model of breast cancer metastasis. J Med Chem. 54:1896–1902. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Draoui N and Feron O: Lactate shuttles at a glance: From physiological paradigms to anti-cancer treatments. Dis Model Mech. 4:727–732. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Zheng J: Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review). Oncol Lett. 4:1151–1157. 2012.PubMed/NCBI

23 

Touisni N, Maresca A, McDonald PC, Lou Y, Scozzafava A, Dedhar S, Winum JY and Supuran CT: Glycosyl coumarin carbonic anhydrase IX and XII inhibitors strongly attenuate the growth of primary breast tumors. J Med Chem. 54:8271–8277. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Klier M, Andes FT, Deitmer JW and Becker HM: Intracellular and extracellular carbonic anhydrases cooperate non-enzymatically to enhance activity of monocarboxylate transporters. J Biol Chem. 289:2765–2775. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Ditte Z, Ditte P, Labudova M, Simko V, Iuliano F, Zatovicova M, Csaderova L, Pastorekova S and Pastorek J: Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa tumor xenografts. BMC Cancer. 14:3582014. View Article : Google Scholar : PubMed/NCBI

26 

Lim KS, Lim KJ, Price AC, Orr BA, Eberhart CG and Bar EE: Inhibition of monocarboxylate transporter-4 depletes stem-like glioblastoma cells and inhibits HIF transcriptional response in a lactate-independent manner. Oncogene. 33:4433–4441. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Kim MY, Zhang T and Kraus WL: Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes Dev. 19:1951–1967. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Zanke BW, Lee C, Arab S and Tannock IF: Death of tumor cells after intracellular acidification is dependent on stress-activated protein kinases (SAPK/JNK) pathway activation and cannot be inhibited by Bcl-2 expression or interleukin 1beta-converting enzyme inhibition. Cancer Res. 58:2801–2808. 1998.PubMed/NCBI

29 

Lagadic-Gossmann D, Huc L and Lecureur V: Alterations of intracellular pH homeostasis in apoptosis: Origins and roles. Cell Death Diff. 11:953–961. 2004. View Article : Google Scholar

30 

Thammasit P, Sangboonruang S, Suwanpairoj S, Khamaikawin W, Intasai N, Kasinrerk W, Tayapiwatana C and Tragoolpua K: Intracellular Acidosis promotes mitochondrial apoptosis pathway: Role of EMMPRIN down-regulation via specific single-chain Fv intrabody. J Cancer. 6:276–286. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jeong KY, Mander P, Sim JJ and Kim HM: Combination of lactate calcium salt with 5‑indanesulfonamide and α‑cyano‑4‑hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification. Oncol Lett 11: 1866-1872, 2016.
APA
Jeong, K., Mander, P., Sim, J.J., & Kim, H.M. (2016). Combination of lactate calcium salt with 5‑indanesulfonamide and α‑cyano‑4‑hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification. Oncology Letters, 11, 1866-1872. https://doi.org/10.3892/ol.2016.4137
MLA
Jeong, K., Mander, P., Sim, J. J., Kim, H. M."Combination of lactate calcium salt with 5‑indanesulfonamide and α‑cyano‑4‑hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification". Oncology Letters 11.3 (2016): 1866-1872.
Chicago
Jeong, K., Mander, P., Sim, J. J., Kim, H. M."Combination of lactate calcium salt with 5‑indanesulfonamide and α‑cyano‑4‑hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification". Oncology Letters 11, no. 3 (2016): 1866-1872. https://doi.org/10.3892/ol.2016.4137
Copy and paste a formatted citation
x
Spandidos Publications style
Jeong KY, Mander P, Sim JJ and Kim HM: Combination of lactate calcium salt with 5‑indanesulfonamide and α‑cyano‑4‑hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification. Oncol Lett 11: 1866-1872, 2016.
APA
Jeong, K., Mander, P., Sim, J.J., & Kim, H.M. (2016). Combination of lactate calcium salt with 5‑indanesulfonamide and α‑cyano‑4‑hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification. Oncology Letters, 11, 1866-1872. https://doi.org/10.3892/ol.2016.4137
MLA
Jeong, K., Mander, P., Sim, J. J., Kim, H. M."Combination of lactate calcium salt with 5‑indanesulfonamide and α‑cyano‑4‑hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification". Oncology Letters 11.3 (2016): 1866-1872.
Chicago
Jeong, K., Mander, P., Sim, J. J., Kim, H. M."Combination of lactate calcium salt with 5‑indanesulfonamide and α‑cyano‑4‑hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification". Oncology Letters 11, no. 3 (2016): 1866-1872. https://doi.org/10.3892/ol.2016.4137
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