Verapamil Inhibits the Respiration Rate of Cancer Cells

  • P. Vaupel
  • W. Mueller-Klieser
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 200)


Calcium antagonists have successfully been used in the treatment of hypertension, cardiac arrhythmias and coronary heart disease. Recent evidence has suggested that such agents may also play a role in the treatment of malignant tumors. Verapamil, a calcium entry blocker, has been reported to enhance the cytotoxicity of several anticancer drugs under in vitro- and in vivo-conditions [1–10]. The effects observed could be explained by an enhanced drug accumulation due to a Verapamil-induced inhibition of the drug efflux from the cancer cells.


Calcium Antagonist Antineoplastic Agent Ehrlich Ascites Carcinoma Calcium Entry Blocker Human Bladder Cancer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Tsuruo, T., Iida, H., Tsukagoshi, S., and Sakurai, Y., 1981, Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil, Cancer Res., 41: 1967–1972.PubMedGoogle Scholar
  2. 2.
    Tsuruo, T., Iida, H., Tsukagoshi, S., and Sakurai, Y., 1982, Increased accumulation of vincristine and adriamycin in drug-resistant P388 tumor cells following incubation with calcium antagonists and calmodulin inhibitors, Cancer Res., 42: 4730–4733.PubMedGoogle Scholar
  3. 3.
    Tsuruo, T., Iida, H., Naganuma, K., Tsukagoshi, S., and Sakurai, Y., 1983, Promotion by verapamil of vincristine responsiveness in tumor cell lines inherently resistant to the drug. Cancer Res., 43: 808–813.PubMedGoogle Scholar
  4. 4.
    Rogan, A.M., Hamilton, T.C., Young, R.C., Klecker, R.W., and Ozols, R.F., 1984, Reversal of adriamycin resistance by verapamil in human ovarian cancer, Science, 224: 994–996.PubMedCrossRefGoogle Scholar
  5. 5.
    Tsuruo, T., Iida, H., Tsukagoshi, S., and Sakurai, Y., 1983, Potentiation of vincristine and adriamycin effects in human hemopoietic tumor cell lines by calcium antagonists and calmodulin inhibitors, Cancer Res., 43: 2267–2272.PubMedGoogle Scholar
  6. 6.
    Slater, L.M., Murray, S.K., and Wetzel, M.W., 1982, Verapamil restoration of daunorubicin responsiveness in daunorubicin-resistant Ehrlich ascites carcinoma, J. Clin. Invest., 70: 1131–1134.PubMedCrossRefGoogle Scholar
  7. 7.
    Simpson, W.G., Tseng, M.T., Anderson, K.C., and Harty, J.I., 1984, Verapamil enhancement of chemotherapeutic efficacy in human bladder cancer cells. J. Urol., 132: 574–576.PubMedGoogle Scholar
  8. 8.
    Helson, L., Member, B., and Helson, C., 1984, Importance of clinical exposure on verapamil enhancement of adriamycine-vincristine cytotoxicity in human neuroblastoma, Cancer Drug Delivery, 1: 303–305.PubMedCrossRefGoogle Scholar
  9. 9.
    Mizuno, S., and Ishida, A., 1982, Potentiation of bleomycin cytotoxicity by membrane-interacting drugs and increased calcium ions, Biochem. Biophys. Res. Commun., 107:Google Scholar
  10. 10.
    Helson, L., 1984, Calcium channel blocker enhancement of anticancer drug cytotoxicity–A review, Cancer Drug Delivery, 1: 353–361.PubMedCrossRefGoogle Scholar
  11. 11.
    Tsuruo, T., Iida, H., Makishima, F., Yamori, T., Kawabata, H., and Tsukagoshi, S., 1985, Inhibition of spontaneous and experimental tumor metastasis by the calcium antagonist verapamil, Cancer Chemother. Pharmacol., 14: 30–33.PubMedCrossRefGoogle Scholar
  12. 12.
    Honn, K.V., Onoda, J.M., Diglio, C.A., and Sloane, B.F., 1983, Calcium channel blockers: Potential antimetastatic agents, Proc. Soc. Exp. Biol. Med., 174: 16–19.PubMedGoogle Scholar
  13. 13.
    Kaelin, W.G., Shrivastav, S., and Jirtle, R.L., 1982, Effect of verapamil on malignant tissue blood flow in SMT-2A tumor-bearing rats, Cancer Res., 42: 3944–3949.PubMedGoogle Scholar
  14. 14.
    Kaelin, W.G., Shrivastav, S., and Jirtle, R.L., 1984, Blood flow to primary tumors and lymph node metastases in SMT-2A tumor-bearing rats following intravenous flunarizine, Cancer Res., 44: 896–899.PubMedGoogle Scholar
  15. 15.
    Vaupel, P., 1985, Peculiarities of intratumor pharmacokinetics of antineoplastic agents, in:“The use of rodent tumors in experimental cancer therapy”, R.F. Kallman, ed., Pergamon Press, New York.Google Scholar
  16. 16.
    Teicher, B.A., Lazo, J.S., and Sartorelli, A.C., 1981, Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells, Cancer Res., 41: 73–81.PubMedGoogle Scholar
  17. 17.
    Lang, W., Wolf, H.U., and Zander, R., 1979, A sensitive continuous and discontinuous photometric determination of oxygen, carbon dioxide, and carbon monoxide in gases and fluids, Anal. Biochem., 92: 255–264.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • P. Vaupel
    • 1
  • W. Mueller-Klieser
    • 1
  1. 1.Department of Applied PhysiologyUniversity of MainzMainzGermany

Personalised recommendations