Skip to main content
Log in

Effect of selenite combined with chemotherapeutic agents on the proliferation of human carcinoma cell lines

  • Accelerated Article
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Selenite is frequently used in combination with cancer chemotherapeutic agents to reduce side effects. However, the cytoprotective activity of selenite may also reduce the efficacy of chemotherapeutic drugs on tumor cells. This study was designed to examine the effects of selenite combined with cytotoxic agents used in clinical protocols [e.g., doxorubicine, docetaxel, 5-fluorouracil (5-FU), methotrexate (MTX), mafosphamide, mitomycin C, gemcitabine, etoposide, cisplatin, irinotecan, and oxaliplatin] on the proliferation of various carcinoma cell types. The data demonstrated that selenite had no marked effects on the antiproliferative activity of docetaxel, doxorubicine, 5-FU, MTX, and mafosphamide in MDA-MB-231 breast cancer cells. Likewise, no consistent changes were observed in A549 lung cancer cell proliferation when selenite was combined with cisplatin, etoposide, gemcitabine, or mitomycin C. On the other hand, selenite potentiated the cytotoxicity of 5-FU, oxaliplatin, and irinotecan in HCT116 colon cancer cells by approx 1.1-fold, 2.7-fold, and 2.6-fold, respectively. In SW620 colon cancer cells, selenite induced a 1.5-fold and 4.3-fold increase of the antiproliferative activity of 5-FU and oxaliplatin, respectively. Whereas irinotecan showed no effects on SW620 cell growth, a combination with selenite resulted in 23% inhibition. Our results indicate that selenite did not reduce the antiproliferative activity of chemotherapeutic agents in vitro. In addition, selenite was able to increase the inhibitory activity of docetaxel in A549 lung cancer cells, and of 5-FU, oxaliplatin, and irinotecan in HCT116 and SW620 colon cancer cells implying selenite is potentially useful as an adjuvant chemotherapeutic agent.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. G.F. Combs and W.P. Gray, Chemoprotective agents: selenium, Pharmacol. Ther. 79, 179–192 (1998).

    Article  PubMed  CAS  Google Scholar 

  2. S.W. May, Selenium-based pharmacological agents: an update. Review, Expert. Opin. Investig. Drugs 11, 1261–1269 (2002).

    Article  PubMed  CAS  Google Scholar 

  3. E. Noaman, A.M. Zahran, A.M. Kamal, and M.F. Omran, Vitamin E and selenium administration as a modulator of antioxidant defense system biochemical assessment and modification, Biol. Trace Element Res. 86, 55–64 (2002).

    Article  CAS  Google Scholar 

  4. K.K. Hamilton, Antioxidant supplements during cancer treatments: where do we stand? Clin. J. Oncol. Nurs. 5, 181–182 (2001).

    PubMed  CAS  Google Scholar 

  5. P.B. Caffrey and G.D. Frenkel, Sensitivity of melphalan-resisitant tumors to selenite in vivo. Cancer Lett. 121, 177–180 (1997).

    Article  PubMed  CAS  Google Scholar 

  6. D.E. Brash and P.A. Havre, New careers for antioxidants, Proc. Natl. Acad. Sci. USA 99, 13969–13971 (2002).

    Article  PubMed  CAS  Google Scholar 

  7. P.B. Caffrey and G.D. Frenkel, Selenite cytotoxicity in drug-resistant and non-resistant ovarian tumor cells, Cancer Res. 52, 4812–4816 (1992).

    PubMed  CAS  Google Scholar 

  8. G.D. Frenkel and P.B. Caffrey, A prevention strategy for circumventing drug resistance in cancer chemotherapy, Curr. Pharm. Des. 7, 1595–1614 (2001).

    Article  PubMed  CAS  Google Scholar 

  9. D.G. Menter, A.L. Sabichi, and S.M. Lippman, Selenium effects on prostate cell growth, Cancer Epidem. Biomarkers & Prev. 9, 1171–1182 (2000).

    CAS  Google Scholar 

  10. E.M. van Lieshout, M.P. Ekkel, M.M. Bedaf, W.A. Nijhoff, and W.H. Peters, Effects of dietary anticarcinogens on rat gastrointestinal glutathione peroxidase activity, Oncol. Rep. 5, 959–963 (1998).

    PubMed  Google Scholar 

  11. L. Hosking, R. Whelan, S. Shellard, P. Bedford, and B. Hill, An evaluation of the role of glutathione and its associated enzymes in the expression of differential sensitivities to antitumor agents shown by a range of human tumor cell lines, Biochem. Pharmacol. 40, 1833–1842 (1990).

    Article  PubMed  CAS  Google Scholar 

  12. J.V. Vadgama, Y. Wu, D. Shen, S. Hsia, and J. Block, Effect of selenium in combination with adriamycin or taxol on several different cancer cells, Anticancer Res. 20, 1391–1414 (2000).

    PubMed  CAS  Google Scholar 

  13. P.B. Caffrey and G.D. Frenkel, Selenium compounds prevent the induction of drug resistance by cisplatin in human ovarian tumor xenografts in vivo, Cancer Chemother. Pharmacol. 46, 74–78 (2000).

    Article  PubMed  CAS  Google Scholar 

  14. G.S. Baldew, C.J. van den Hamer, G. Los, N.P. Vermeulen, J.J. de Goeij, and J.G. McVie, Selenium-induced protection against cis-diamminedichloroplatinum(II) nephrotoxicity in mice and rats, Cancer Res. 49, 3020–3023 (1989).

    PubMed  CAS  Google Scholar 

  15. A. Naganuma, M. Satoh, M. Yokoyama, and N. Imura, Selenium efficiently depressed toxic side effect of cis-diamminedichloroplatinum, Res. Commun. Chem. Pathol. Pharmacol. 42, 127–132 (1983).

    PubMed  CAS  Google Scholar 

  16. K. Ohkawa, Y. Tsukada, H. Dohzono, K. Koike, and Y. Terashima, The effects of coadministration of selenium and cisplatin (CDDP) on CDDP-induced toxicity and antitumour activity, Br. J. Cancer 58, 38–41 (1988).

    PubMed  CAS  Google Scholar 

  17. N.P. Vermeulen, G.S. Baldew, G. Los, J.G. McVie, and J.J. De Goeij, Reduction of cisplatin nephrotoxicity by sodium selenite. Lack of interaction at the pharmacokinetic level of both compounds, Drug Metab. Dispos. 21, 30–36 (1993).

    PubMed  CAS  Google Scholar 

  18. Y.J Hu, Y. Chen, Y.Q. Zhang, et al. The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients, Biol. Trace Element Res. 56, 331–341 (1997).

    CAS  Google Scholar 

  19. H. Sundstrom, H. Korpela, E. Sajanti, and A. Kauppila, Supplementation with selenium, vitamin E and their combination in gynaecological cancer during cytotoxic chemotherapy, Carcinogenesis 10, 273–278 (1989).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Harald Heidecke.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schroeder, C.P., Goeldner, E.M., Schulze-Forster, K. et al. Effect of selenite combined with chemotherapeutic agents on the proliferation of human carcinoma cell lines. Biol Trace Elem Res 99, 17–25 (2004). https://doi.org/10.1385/BTER:99:1-3:017

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/BTER:99:1-3:017

Index Entries

Navigation