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Relative cytotoxicities of Adriamycin and epirubicin in combination with lonidamine against human bladder cancer cell lines

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Abstract

We have used a panel of bladder cancer cell lines to compare the toxicities of Adriamycin and epirubicin, two drugs used intravesically to treat superficial transitional cell cancer (TCC) of the bladder, alone and in combination with lonidamine, an agent known to be active against anthracycline-resistant disease. Comparing concentrations reducing colony-forming ability by 50%, epirubicin and Adriamycin were similar in their cytotoxicities, although epirubicin was more potent against every line except an Adriamycin-resistant subline. Combinations of the two drugs with a non-cytotoxic concentration (1 μg/ml) of lonidamine were tested using the Adriamycin-resistant subline MGH-U1R and its sensitive parental line MGH-U1. The addition of lonidamine caused a twofold increase in the sensitivity of the resistant subline to both drugs, while having no effect on the sensitivity of the parental line. The data indicate that this combination might be of value in anthracycline-resistant disease.

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References

  1. Band PR, Maroun J, Pritchard K, Stewart D, Coppin CM, Wilson K, Eisenhauer EA (1986) Phase II study of lonidamine in patients with metastatic breast cancer. Cancer Treat Rep 70:1305

    Google Scholar 

  2. Batist G, Tulpule A, Sinha BK, Katki AG, Myers CE, Cowan KH (1986) Induction of an anionic GSH-S-transferase in multidrug-resistant human breast cancer cells and in xenobiotic-resistant preneoplastic liver nodules induced by carcinogens. J Biol Chem 261:15544

    Google Scholar 

  3. Bertetto O, Villois MT, Valle A, Zerbi R, Clerito M, Calciati A (1987) Phase II study with lonidamine in advanced head and neck (H&N) squamous cell carcinoma. Proc 4th Europ Conf Clin Oncol Nursing Abstract 488, Madrid, Spain

  4. Breau JL, Morere JF, Israel L (1988) Chemotherapy with or without lonidamine for induction therapy in squamous cell carcinoma of the lung. A randomised study comparing cisplatinum-bleomycin or cisplatinum-bleomycin-VP16 213 (±lonidamine). Proc Am Soc Clin Oncol 7:819

    Google Scholar 

  5. Bubenik J, Baresova M, Viklicky V, Jakoubkova J, Sainerova H, Donner J (1973) Established cell line of urinary bladder carcinoma (T24) containing tumour-specific antigen. Int J Cancer 11:765

    Google Scholar 

  6. Caputo A (1981) Preliminary results in some tumor systems with indazole-carboxylic acids. Chemotherapy 27 [Suppl 2]:107

    Google Scholar 

  7. Citro G, Cucco C, Verdina A, Zupi G (1991) Reversal of adriamycin resistance by lonidamine in a human breast cancer cell line. Br J Cancer 64:534

    Google Scholar 

  8. Cividalli A, Gentile PF, Alonzi A, Benassi M, Mauro F, Floridi A (1992) In vivo control of tumor growth by lonidamine and radiations: influence of the timing and sequence of drug administration and irradiation. Int J Oncol 1:561

    Google Scholar 

  9. Clynes M (1993) Cellular models for multiple drug resistance in cancer. In Vitro Cell Dev Biol 29A:171

    Google Scholar 

  10. De Martino C, Battelli T, Paggi MG, Nista A, Marcante ML, D'Atri S, Malorni W, Gallo M, Floridi A (1984) Effects of lonidamine on murine and human tumour cells in vitro. A morphological and biochemical study. Oncology 41 [Suppl 1]:15

    Google Scholar 

  11. Di Marco A (1977) Changes of activity of daunorubicin, adriamycin and stereoisomers following the introduction or removal of hydroxyl groups in the aminosugar moiety. Chem-Biol Interactions 19:291

    Google Scholar 

  12. Di Silverio F, Tenaglia R, Saragnano G, Ciottoli GB, De Gregorio M, Ferraro F (1985) Lonidamine in carcinoma of the prostate. Proc 14th Int Congress Chemotherapy. Recent Adv Chemother 616–618

  13. Fleischmann J, Goldberg G (1993) Management of superficial transitional cell carcinoma of the bladder. Semin Urol 11:193

    Google Scholar 

  14. Floridi A, Paggi MG, D'Atri S, De Martino C, Marcante ML, Silvestrini B, Caputo A (1981) Effects of lonidamine on the energy metabolism of Ehrlich ascites tumor cells. Cancer Res 41:4661

    Google Scholar 

  15. Floridi A, Paggi MG, Marcante ML, Silvestrini B, Caputo A, De Martino C (1981) Lonidamine: a selective inhibitor of aerobic glycolysis of murine tumor cells. J Natl Cancer Inst 66:497

    Google Scholar 

  16. Floridi A, Bagnato A, Bianchi C, Paggi MG, Nista A, Silvestrini B, Caputo A (1986) Kinetics of inhibition of mitochondrial respiration by the antineoplastic agent lonidamine. J Exp Clin Cancer Res 5:273

    Google Scholar 

  17. Floridi A, Bianchi C, Bagnato A, Gambacurta A, Paggi MG, Silvestrini B, Caputo A (1987) Lonidamine-induced outer membrane permeability and susceptibility of mitochondria to inhibition by adriamycin. Anticancer Res 7:1149

    Google Scholar 

  18. Floyd JW, Lin C, Prout GR, Jr (1990) Multi-drug resistance of a doxorubicin-resistant bladder cancer cell line. J Urol 144: 169

    Google Scholar 

  19. Fry AM, Chresta CM, Davies MS, Walker MC, Harris AL, Hartley JA, Masters JRW, Hickson ID (1991) Relationship between topoisomerase II level and chemosensitivity in human tumor cell lines. Cancer Res 51:6592

    Google Scholar 

  20. Giannotti P, Ambrogi F, Ciottoli GB (1984) Lonidamine plus adriamycin versus adriamycin alone in the adjuvant treatment of recurrent papillary carcinomas of the urinary bladder. Oncology 41:104

    Google Scholar 

  21. Groos E, Walker L, Masters JRW (1986) Intravesical chemotherapy: studies on the relationship between pH and cytotoxicity. Cancer 58:1199

    Google Scholar 

  22. Hahn GM, Van Karsen I, Silvestrini B (1984) Inhibition of the recovery from potentially lethal damage by lonidamine. Br J Cancer 50:657

    Google Scholar 

  23. Heywood R, James RW, Scorza Barcellona P, Campana A, Cioli V (1981) Toxicological studies on 1-substituted-indazole-3-carboxylic acids. Chemotherapy 27 [Suppl 2]:91

    Google Scholar 

  24. Juliano RA, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152

    Google Scholar 

  25. Kaye SB (1993) P glycoprotein (P-gp) and drug resistance-time for reappraisal? Br J Cancer 67:641

    Google Scholar 

  26. Kim JH, Alfieri A, Kim SH, Young CW, Silvestrini B (1984) Radiosensitization of meth-A fibrosarcoma in mice by lonidamine. Oncology 41 [Suppl 1]:36

    Google Scholar 

  27. Kim JH, Kim SH, Alfieri A, Young CW, Silvestrini B (1984) Lonidamine: a hyperthermic sensitizer of HeLa cells in culture and of the meth-A tumor in vivo. Oncology 41 [Suppl 1]:30

    Google Scholar 

  28. Kim JH, Alfieri A, Kim SH, Young CW (1986) The potentiation of radiation effects on two murine tumors by lonidamine. Cancer Res 46:1120

    Google Scholar 

  29. Kokron O, Maca S, De Gregorio M, Ciottoli GB (1990) Phase II study of lonidamine in non-small cell lung cancer. Br J Cancer 61:316

    Google Scholar 

  30. Long JP, Jr, Prout GR, Jr, Wong YK, Lin C (1990) The effect of verapamil on a multi-drug resistant bladder carcinoma cell line and its potential as an intravesical chemotherapeutic agent. J Urol 143:1053

    Google Scholar 

  31. Lukkarinen O, Paul C, Hellstrom P, Kontturi M, Nurmi M, Puntala P, Ottelin J, Tammela T, Tidefeldt U (1991) Intravesical epirubicin with and without verapamil for the prophylaxis of superficial bladder tumours. Scand J Urol Nephrol 25:25

    Google Scholar 

  32. Lum BL (1983) Intravesical chemotherapy of superficial bladder cancer. Recent Results Cancer Res 85:3

    Google Scholar 

  33. Lum BL, Torti FM (1991) Adjuvant intravesicular pharmacotherapy for superficial bladder cancer. J Natl Cancer Inst 83:682

    Google Scholar 

  34. Magno L, Terraneo F, Bertoni F, Tordiglione M, Bardelli D, Rosignoli MT, Ciotolli GB (1994) Double-blind randomized study of lonidamine and radiotherapy in head and neck cancer. Int J Radiat Oncol Biol Phys 29:45

    Google Scholar 

  35. Mansi JL, de Graeff A, Newell DR, Glaholm J, Button D, Leach MO, Payne G, Smith IE (1991) A phase II clinical and pharmokinetic study of lonidamine in patients with advanced breast cancer. Br J Cancer 64:593

    Google Scholar 

  36. Masters JRW, Hepburn PJ, Walker L, Highman WJ, Trejdosiewicz LK, Povey S, Parkar M, Hill BT, Riddle PR, Franks LM (1986) Tissue culture model of transitional cell carcinoma: characterization of twenty-two human urothelial cell lines. Cancer Res 46:3630

    Google Scholar 

  37. McGovern F, Kachel T, Vijan S, Schiff S, Lin C, Prout GR Jr (1988) Establishment and characterization of a doxorubicin resistant human bladder cancer cell line (MGH-U1R). J Urol 140:410

    Google Scholar 

  38. Mickisch GH, Merlino GT, Galski H, Gottesman MM, Pastan I (1991) Transgenic mice that express the human multidrug-resistance gene in bone marrow enable a rapid identification of agents that reverse drug resistance. Proc Natl Acad Sci 88:547

    Google Scholar 

  39. Naito S, Kimiya K, Ueda T, Kumazawa J, Omoto T, Osada Y, Iguchi A, Ariyoshi A, Sagiyama K (1992) Intravesical therapy with adriamycin plus verapamil in patients with superficial bladder cancer: a pilot study. Urol Int 48:270

    Google Scholar 

  40. Newell DR, Mansi J, Hardy J, Button D, Jenns K, Smith IE, Picollo R, Catanese B (1991) The pharmacokinetics of oral lonidamine in breast and lung cancer patients. Semin Oncol 18:11

    Google Scholar 

  41. Pronzato P, Amoroso D, Bertelli G, Conte PF, Cusimano MP, Ciotolli GB, Gulisano M, Lionetto R (1989) Phase II study of lonidamine in metastatic breast cancer. Br J Cancer 59:251

    Google Scholar 

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

    Google Scholar 

  43. Raderer M, Scheithauer W (1993) Clinical trials of agents that reverse multidrug resistance. Cancer 72:3553

    Google Scholar 

  44. Rasheed S, Gardner MB, Rongey RW, Nelson-Rees WA, Arnstein P (1977) Human bladder carcinoma: characterization of two new tumor cell lines and search for tumor viruses. J Natl Cancer Inst 58:881

    Google Scholar 

  45. Rigby CC, Franks LM (1970) A human tissue culture cell line from a transitional cell tumour of the urinary bladder: growth, chromosome pattern and ultrastructure. Br J Cancer 24:746

    Google Scholar 

  46. Scagliotti GV, Gozzellino F, Albera C, Pescetti G (1989) Chronic administration of lonidamine in untreated non-small cell lung cancer of Stage III M0–1. Chemotherapy 35:64

    Google Scholar 

  47. Shinohara N, Liebert M, Wedemeyer G, Chang JHC, Grossman HB (1993) Evaluation of multiple drug resistance in human bladder cancer cell lines. J Urol 150:505

    Google Scholar 

  48. Silvestrini B, Hahn GM, Cioli V, De Martino C (1983) Effects of lonidamine alone or combined with hyperthermia in some experimental cell and tumor systems. Br J Cancer 47:221

    Google Scholar 

  49. Silvestrini R, Zaffaroni N, Villa R, Orlandi L, Costa A (1992) Enhancement of cisplatin activity by lonidamine in human ovarian cancer cells. Int J Cancer 52:813

    Google Scholar 

  50. Stewart BH, Branson AC, Hewitt CB, Kiser WS, Straffon RA (1972) The treatment of patients with interstitial cystitis with special reference to intravesical DMSO. J Urol 107:377

    Google Scholar 

  51. Stewart DJ, Evans WK (1989) Non-chemotherapeutic agents that potentiate chemotherapy efficacy. Cancer Treat Rev 16:1

    Google Scholar 

  52. Williams RD (1980) Human urologic cancer cell lines. Invest Urol 17:359

    Google Scholar 

  53. Zupi G, Greco C, Laudonio N, Benassi M, Silvestrini B, Caputo A (1986) In vitro and in vivo potentiation by lonidamine of the antitumour effect of adriamycin. Anticancer Res 6:1245

    Google Scholar 

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Authors and Affiliations

  1. Department of Urology, King's College Hospital, SE5 9RS, London, UK

    R. J. M. Popert & M. Coptcoat

  2. Institute of Urology and Nephrology, 3rd Floor Research Laboratories, University College London, 67 Riding House Street, W1P 7PN, London, UK

    J. R. W. Masters

  3. Laboratory Experimental Chemotherapy, Instituto Regina Elena, Via delle Messi d'Oro 156, 00158, Rome, Italy

    G. Zupi

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  1. R. J. M. Popert
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  2. J. R. W. Masters
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  3. M. Coptcoat
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  4. G. Zupi
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Popert, R.J.M., Masters, J.R.W., Coptcoat, M. et al. Relative cytotoxicities of Adriamycin and epirubicin in combination with lonidamine against human bladder cancer cell lines. Urol. Res. 22, 367–372 (1995). https://doi.org/10.1007/BF00296877

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  • DOI: https://doi.org/10.1007/BF00296877

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