Skip to main content

In vitro potentiation by lonidamine of the cytotoxic effect of adriamycin on primary and established breast cancer cell lines

Breast Cancer Research and Treatment volume 24, pages 27–34 (1992)Cite this article

Summary

Lonidamine is a new potential chemotherapeutic agent, relatively non-toxic, that can positively modulate the efficacy of several antineoplastic drugs. We evaluated the response of two established human breast cancer cell lines (MCF-7 and BRC-230) and of 20 primary breast cancer cell lines to lonidamine, either alone or in combination with adriamycin, the drug most widely used in the management of breast cancer. Different schedules were tested by varying either concentration of the drugs (LND: 10–150µg/ml; ADM: 0.10–0.15µg/ml), or time of exposure (1–96 hours), or sequence of administration (ADM → LND; LND → ADM; ADM + LND). Our results indicate slight sensitivity of the cell lines to lonidamine when used alone, whereas an increase of efficacy was noted when lonidamine was added for at least 24 hours after a 4 hour exposure to adriamycin. Such efficacy was significantly greater than that expected from an additive effect between the two drugs. We conclude that lonidamine, when given according to an appropriate schedule, enhances,in vitro, the efficacy of adriamycin. A correct employment of lonidamine in the management of breast cancer might therefore potentiate the therapeutic effect of adriamycin.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Floridi A, De Martino C, Marcante ML, Bellocci M, Apollonj C, Scorza Barcellona P, Silvestrini B: Morphological and biochemical modifications of rat germ cell mitochondria induced by new antispermatogenic compounds: studiesin vivo andin vitro. Exp Mol Pathol 35: 314–331, 1981

    PubMed  Google Scholar 

  2. De Martino C, Floridi A, Marcante ML, Malorni W, Scorza Barcellona P, Bellocci M, Silvestrini B: Morphological, histochemical and biochemical studies on germ cell mitochondria of normal rats. Cell Tissue Res 196: 1–22, 1979

    PubMed  Google Scholar 

  3. Caputo A, Floridi A, Paggi MG, Marcante ML, De Martino C, Silvestrini B: Control of cell differentiation and cancer cells by lonidamine. Chemother Oncol 3: 276–281, 1979

    Google Scholar 

  4. Floridi A, Bellocci M, Paggi MG, Marcante ML, De Martino C: Changes of energy metabolism in the germ cells and Ehrlich ascites tumour cells. Chemotherapy 27 (Suppl 2): 50–60, 1981

    PubMed  Google Scholar 

  5. Floridi A, Paggi MG, Marcante ML, Silvestrini B, Caputo A, De Martino C: Lonidamine, a selective inhibitor of aerobic glycolysis of murine tumour cells. J Natl Cancer Inst 66: 497–499, 1981

    PubMed  Google Scholar 

  6. Floridi A, Paggi MG, D'Atri S, De Martino C, Marcante ML, Silvestrini B, Caputo A: Effect of lonidamine on the energy metabolism of Ehrlich ascites tumour cells. Cancer Res 41: 4661–4666, 1981

    PubMed  Google Scholar 

  7. Floridi A, Lehninger AL: Action of the antitumour and antispermatogenic agent lonidamine on electron transport in Ehrlich ascites tumour mitochondria. Arch Biophys 226: 73–83, 1983

    Google Scholar 

  8. De Martino C, Malorni W, Accinni L, Rosati F, Nista A, Fornisano G, Silvestrini B, Arancia B: Cell membrane changes induced by lonidamine in human erythrocytes and T-lymphocytes, and Ehrlich ascites tumour cells. Exp Mol Path 46: 15–30, 1987

    Google Scholar 

  9. Floridi A, Gambacurta A, Bagnato A, Bianchi C, Paggi MG, Silvestrini B, Caputo A: Modulation of adriamycin uptake by lonidamine in Ehrlich ascites tumour cells. Exp Mol Path 49: 421–423, 1988

    Google Scholar 

  10. De Martino C, Battelli T, Paggi MG, Nista A, Marcante ML, D'Arti S, Malorni W, Gallo M, Floridi A: Effects of lonidamine on murine and human tumour cellsin vitro. A morphological and biochemical study. Oncology 41: 15–29, 1984

    PubMed  Google Scholar 

  11. Silvestrini B, Hahn GM, Cioli V, De Martino C: Effects of lonidamine alone or combined with hyperthermia in some experimental cell and tumour systems. Brit J Cancer 47: 221–231, 1983

    PubMed  Google Scholar 

  12. Zupi G, Greco C, Laudonio N, Benassi M, Silvestrini B, Caputo A:In vitro andin vivo potentiation by lonidamine of the antitumor effect of adriamycin. Anticancer Res 6: 1245–1250, 1986

    PubMed  Google Scholar 

  13. Rotin D, Tannock IF: The effect of the drug lonidamine on chinese hamster ovary cellsin vitro and on experimental tumors. Int J Radiat Oncol Biol Phys 10: 1595–1598, 1984

    PubMed  Google Scholar 

  14. Kim JH, Kim SH, He SQ, Alfieri AA, Young CW: Potentiation of radiation effects on multicellular tumor spheroids (MTS) of He-La cells by lonidamine. Int J Radiat Oncol Biol Phys 16: 1277–1280, 1989

    PubMed  Google Scholar 

  15. Starace G, Badaracco A, Bertuzzi A, Gandolfi A, Greco C, Totaro MD, Vitelli R, Zupi G: Kinetic and survival response of the M14 cell line to lonidamine associated with adriamycin or hyperthermia. J Cancer Res Clin Oncol 113: 451–458, 1987

    PubMed  Google Scholar 

  16. Hahn GM, Van Kersen I, Silvestrini B: Inhibition of the recovery from potentially lethal damage by lonidamine. Brit J Cancer 50: 657–660, 1984

    PubMed  Google Scholar 

  17. Kim JH, Alfieri AA, Kim SH, Young CW: Potentiation of radiation effects on two murine tumors by lonidamine. Cancer Res 46: 1120–1123, 1986

    PubMed  Google Scholar 

  18. De Fabritiis P, Sandrelli A, Covelli A, Simone F, De Felice L, Pulsoni A, Zupi G, Mandelli F:In vitro pharmacological purging of human bone marrow is enhanced by the use of lonidamine. Exp Mol Path 50: 210–219, 1989

    Google Scholar 

  19. Chitnis M, Adwankar M: Potentiation of adriamycin cytoxicity in P388 murine leukemia sensitive and resistant to adriamycin by use of lonidamine and hyperthermia. Tumori 72: 469–473, 1986

    PubMed  Google Scholar 

  20. Rosbe KW, Brann TW, Holden SA, Teicher BA, Frei E: Effect of lonidamine on the cytotoxicity of four alkylating agentsin vitro. Cancer Chemother Pharmacol 12: 284–291, 1989

    Google Scholar 

  21. Bellelli A, Bellelli L, Di Palma M, Lorenzon I, Mattioni M, Nista A, Pavese I, Rusconi V, Serri M: Effects of VM26 and lonidamine on a 316 melanoma cell line. In press, 1990

  22. Raaphorst GP, Feeley MM, Heller DP, Danjoux CE, Martin L, Maroun JA, De Sanctis AJ: Lonidamine can enhance the cytotoxic effect of cisplatin in human tumor cells and rodent cells. Anticancer Res 10: 923–928, 1990

    PubMed  Google Scholar 

  23. Teicher BA, Herman TS, Holden SA, Epelbaum R, Liu S, Frei E: Lonidamine as a modulator of alkylating agent activityin vitro andin vivo. Cancer Res 51: 780–784, 1991

    PubMed  Google Scholar 

  24. Smith HS, Lan S, Ceriani R, Hackett AJ, Stampfer MR: Clonal proliferation of cultured nonmalignant and malignant human breast epithelia. Cancer Res 41: 4637–4643, 1981

    PubMed  Google Scholar 

  25. Smith HS, Hackett AJ, Lan S, Stampfer MR: Use of an efficient method for culturing human mammary epithelial cells to study adriamycin sensitivity. Cancer Chemother Pharmacol 6: 237–244, 1981

    PubMed  Google Scholar 

  26. Smith HS, Lippman ME, Hiller AJ, Stampfer MR, Hackett AJ: Response to doxorubicin of cultured normal and cancerous human mammary epithelial cells. J Natl Cancer Inst 74: 341–347, 1985

    PubMed  Google Scholar 

  27. Smith HS, Zoli W, Volpi A, Hiller A, Lippman M, Swain S, Mayall B, Dollbaum C, Hackett AJ, Amadori D: Preliminary correlations of clinical outcome within vitro chemosensitivity of second passage human breast cancer cells. Cancer Res 50: 2943–2948, 1990

    PubMed  Google Scholar 

  28. Stampfer MR, Hallowes RC, Hackett AJ: Growth of normal human mammary cells in culture. In Vitro 16: 415–425, 1980

    PubMed  Google Scholar 

  29. Zoli W, Volpi A, Bonaguri C, Riccobon A, Savini S, Brizio R, Saragoni A, Medri L, Marra GA, Amadori D: An efficient method for culturing human breast carcinoma to evaluate antiblastic drug activityin vitro: experience on 136 primary cancers and on 116 recurrences. Breast Cancer Res Treat 17: 231–238, 1990

    Google Scholar 

  30. E.O.R.T.C. Breast Cancer Cooperative Group: Revision of the standards for the assessment of the hormone receptors in human breast cancer. Eur J Cancer 16: 1513–1515, 1980

    Google Scholar 

  31. Drewinko B, Loo TL, Brown B, Gottlieb JA, Freireich EJ: Combination chemotherapyin vitro with adriamycin. Observations of additive, antagonistic, and synergistic effects when used in two-drug combinations on cultured human lymphoma cells. Cancer Biochem Biophys 1: 187–195, 1976

    PubMed  Google Scholar 

  32. Kendall MG, Stuart A: The Advanced Theory of Statistics. Hafner Publishing Co, New York, 1983: Vol I, Section 10.6; Vol. II, Chaps 17 & 18

    Google Scholar 

  33. Sobrero A: Attività antitumorale della lonidamina: risultatiin vitro. In: Rosso R, Vitale V (eds) Lonidamina. Scuola Superiore di Oncologia e Scienze Biomediche, 1990, pp 20–34

  34. Rossi V, Caricato L, Jocicevic L, Ciarniello MG, Caranti S: Anin vitro study of lonidamine with cytotoxic drugs on MCF7 adenocarcinoma line (abstract). J Cancer Res Clin Oncol 116 (Suppl, part 1): 25, 1990

    Google Scholar 

  35. Cucco C, Verdina G, Citro G, Zupi G: Lonidamine activity on MCF7 adriamycin resistant cells (abstract). J Cancer Res Clin Oncol 116 (suppl, part 1): 620, 1990

    Google Scholar 

Download references

Author information

Affiliations

  1. Oncological Department, Morgagni-Pierantoni Hospital, U.S.L. 38, Viale Forlanini, 47100, Forli, Italy

    Saverio Savini, Wainer Zoli, Oriana Nanni, Annalisa Volpi, G. Luca Frassineti, Alberto Flamigni & Dino Amadori

  2. Division of General Surgery, Morgagni-Pierantoni Hospital, U.S.L. 38, Forli, Italy

    Enrico Magni

  3. Reproductive Medicine Unit, Department of Obstetrics and Gynecology, University of Bologna, Bologna, Italy

    Andrea Amadori

Authors
  1. Saverio Savini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wainer Zoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oriana Nanni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Annalisa Volpi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Luca Frassineti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Enrico Magni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alberto Flamigni
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrea Amadori
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dino Amadori
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Savini, S., Zoli, W., Nanni, O. et al. In vitro potentiation by lonidamine of the cytotoxic effect of adriamycin on primary and established breast cancer cell lines. Breast Cancer Res Tr 24, 27–34 (1992). https://doi.org/10.1007/BF01832355

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01832355

Key words

  • adriamycin
  • breast cancer
  • chemosensitivity assay
  • lonidamine