Lonidamine induces intracellular tumor acidification and ATP depletion in breast, prostate and ovarian cancer xenografts and potentiates response to doxorubicin

NMR in Biomedicine

Volumn 28, Issue 3, 2015, Pages 281-290

  Nath, Kavindra ^a   Nelson, David S ^a   Heitjan, Daniel F ^b   Leeper, Dennis B ^c   Zhou, Rong ^a   Glickson, Jerry D ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

Doxorubicin; Lonidamine; Monocarboxylate acid transport inhibitor; Tumor acidification; Tumor de energization

Indexed keywords

ACIDIFICATION; ACTIVATION ANALYSIS; CALCIUM COMPOUNDS; CARBOXYLIC ACIDS; CELLS; CYTOLOGY; DERMATOLOGY; ONCOLOGY; TUMORS; UROLOGY;

ACID TRANSPORT; CLINICAL TREATMENTS; DOXORUBICIN; ENERGIZATION; INORGANIC PHOSPHATES; LONIDAMINE; MONOTONIC DECREASE; THERAPEUTIC PROCEDURES;

DISEASES;

ADENOSINE TRIPHOSPHATE; ANTHRACYCLINE; DOXORUBICIN; LONIDAMINE; MELPHALAN; NUCLEOSIDE TRIPHOSPHATE; PHOSPHATE; ACID; COTRANSPORTER; INDAZOLE DERIVATIVE; MONOCARBOXYLATE TRANSPORT PROTEIN 1; MONOCARBOXYLATE TRANSPORTER;

ACIDIFICATION; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOENERGY; BREAST CANCER; BREAST CARCINOMA; CANCER INHIBITION; CELL KILLING; CELL PH; DRUG POTENTIATION; FEMALE; HUMAN; MALE; MELANOMA; MOUSE; NONHUMAN; OVARY CANCER; PH; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN DEPLETION; RADIOSENSITIVITY; TUMOR MICROENVIRONMENT; TUMOR XENOGRAFT; WEIGHT REDUCTION; ANIMAL; BREAST TUMOR; CELL PROLIFERATION; CELL SURVIVAL; DEFICIENCY; DRUG EFFECTS; DRUG SCREENING; ENERGY METABOLISM; INTRACELLULAR SPACE; METABOLISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; NUDE MOUSE; OVARY TUMOR; PATHOLOGY; PROSTATE TUMOR; TUMOR CELL LINE; WESTERN BLOTTING;

BRASSICACEAE;

ACIDS; ADENOSINE TRIPHOSPHATE; ANIMALS; BLOTTING, WESTERN; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; DOXORUBICIN; DRUG SYNERGISM; ENERGY METABOLISM; FEMALE; HUMANS; HYDROGEN-ION CONCENTRATION; INDAZOLES; INTRACELLULAR SPACE; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MICE, NUDE; MONOCARBOXYLIC ACID TRANSPORTERS; OVARIAN NEOPLASMS; PROSTATIC NEOPLASMS; SYMPORTERS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84924064231     PISSN: 09523480     EISSN: 10991492     Source Type: Journal    
DOI: 10.1002/nbm.3240     Document Type: Article

References (47)

1. 13C nuclear magnetic resonance studies. Cancer Res. 1995; 55(13): 2814-2821.
2. Ben-Yoseph O, Lyons JC, Song CW, Ross BD. Mechanism of action of lonidamine in the 9L brain tumor model involves inhibition of lactate efflux and intracellular acidification. J. Neurooncol 1998; 36(2): 149-157.
3. Mardor Y, Kaplan O, Sterin M, Ruiz-Cabello J, Ash E, Roth Y, Ringel I, Cohen JS. Noninvasive real-time monitoring of intracellular cancer cell metabolism and response to lonidamine treatment using diffusion weighted proton magnetic resonance spectroscopy. Cancer Res. 2000; 60(18): 5179-5186.
4. 1H MRS of DB-1 melanoma xenografts: lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan. NMR Biomed. 2013; 26(1): 98-105.
5. Zhou R, Bansal N, Leeper DB, Pickup S, Glickson JD. Enhancement of hyperglycemia-induced acidification of human melanoma xenografts with inhibitors of respiration and ion transport. Acad. Radiol. 2001; 8(7): 571-582.
6. Kuin A, Aalders M, Lamfers M, van Zuidam DJ, Essers M, Beijnen JH, Smets LA. Potentiation of anti-cancer drug activity at low intratumoral pH induced by the mitochondrial inhibitor m-iodobenzylguanidine (MIBG) and its analogue benzylguanidine (BG). Br. J. Cancer 1999; 79(5/6): 793-801.
7. Wong P, Lee C, Tannock IF. Reduction of intracellular pH as a strategy to enhance the pH-dependent cytotoxic effects of melphalan for human breast cancer cells. Clin. Cancer Res. 2005; 11(9): 3553-3557.
8. Kim JH, Kim SH, Alfieri A, Young CW, Silvestrini B. Lonidamine: a hyperthermic sensitizer of HeLa cells in culture and of the Meth-A tumor in vivo. Oncology 1984; 41: 30-35.
9. Ning SC, Hahn GM. Combination therapy: lonidamine, hyperthermia, and chemotherapy against the RIF-1 tumor in vivo. Cancer Res. 1991; 51(21): 5910-5914.
10. Silvestrini B, Hahn GM, Cioli V, Demartino C. Effects of lonidamine alone or combined with hyperthermia in some experimental cell and tumor systems. Br. J. Cancer 1983; 47(2): 221-231.
11. Teicher BA, Holden SA, Ara G, Menon K. Whole-body hyperthermia and lonidamine as adjuvant therapy to treatment with cisplatin with or without local radiation in mouse bearing the Lewis lung-carcinoma. Int. J. Hyperth. 1995; 11(5): 637-645.
12. Coss RA, Storck CW, Wells TC, Kulp KA, Wahl M, Leeper DB. Thermal sensitisation by lonidamine of human melanoma cells grown at low extracellular pH. Int. J. Hyperth. 2014; 30(1): 75-78.
13. Kim JH, Alfieri AA, Kim SH, Young CW. Potentiation of radiation effects on 2 murine tumors by lonidamine. Cancer Res. 1986; 46(3): 1120-1123.
14. Hill LL, Korngold R, Jaworsky C, Murphy G, McCue P, Berd D. Growth and metastasis of fresh human melanoma tissue in mice with severe combined immunodeficiency. Cancer Res. 1991; 51(18): 4937-4941.
15. Li ZJ, Qiao H, Lebherz C, Choi SR, Zhou XY, Gao GP, Kung HF, Rader DJ, Wilson JM, Glickson JD, Zhou R. Creatine kinase, a magnetic resonance-detectable marker gene for quantification of liver-directed gene transfer. Human Gene Ther. 2005; 16(12): 1429-1438.
16. 31P nuclear magnetic resonance spectroscopy studies of tumor energy metabolism and its relationship to intracapillary oxyhemoglobin saturation status and tumor hypoxia. Cancer Res. 1988; 48(19): 5440-5446.
17. 2H NMR spectroscopy using water as an internal intensity reference. Magn. Reson. Med. 1992; 28(1): 105-121.
18. Corbett TH, Valeriote FA. Rodent models in experimental chemotherapy. In The Use of Rodent Tumors in Experimental Cancer Therapy: Conclusions and Recommendations, Kallman RF (ed.). Pergamon: New York, 1987, 233-247.
19. Efron B, Tibshirani T. Bootstrap method for standard errors, confidence intervals, and other measures of statistical accuracy. Stat. Sci. 1986; 1(1): 54-77.
20. Wahl ML, Owen JA, Burd R, Herlands RA, Nogami SS, Rodeck U, Berd D, Leeper DB, Owen CS. Regulation of intracellular pH in human melanoma: potential therapeutic implications. Mol. Cancer Ther. 2002; 1(8): 617-628.
21. Cioli V, Bellocci B, Putzolu S, Malorni W, Demartino C. Anti-spermogenic activity of lonidamine (AF-1890) in rabbit. Ultramicroscopy 1980; 5(3): 418-418.
22. Pacilio G, Carteni G, Biglietto M, Decesare M. Lonidamine alone and in combination with other chemotherapeutic-agents in the treatment of cancer-patients. Oncology 1984; 41: 108-112.
23. Amadori D, Frassineti GL, De Matteis A, Mustacchi G, Santoro A, Cariello S, Ferrari M, Nascimben O, Nanni O, Lombardi A, Scarpi E, Zoli W. Modulating effect of lonidamine on response to doxorubicin in metastatic breast cancer patients: results from a multicenter prospective randomized trial. Breast Cancer Res. Treat. 1998; 49(3): 209-217.
24. Buccheri G, Ferrigno D. A randomised trial of MACC chemotherapy with or without lonidamine in advanced non-small cell lung cancer. Cuneo Lung Cancer Study Group (CuLCaSG). Eur. J. Cancer 1994; 30A(10): 1424-1431.
25. Robins HI, Longo WL, Steeves RA, Cohen JD, Schmitt CL, Neville AJ, Okeefe S, Lagoni R, Riggs C. Adjunctive therapy (whole-body hyperthermia versus lonidamine) to total-body irradiation for the treatment of favorable B-cell neoplasms - a report of 2 pilot clinical-trials and laboratory investigations. Int. J. Radiat. Oncol. Biol. Phys. 1990; 18(4): 909-920.
26. Roehrborn CG. The development of lonidamine for benign prostatic hyperplasia and other indications. Rev. Urol. 2005; 7(Suppl. 7): S12-S20.
27. Robins HI, Longo WL, Lagoni RK, Neville AJ, Hugander A, Schmitt CL, Riggs C. Phase-I trial of lonidamine with whole-body hyperthermia in advanced cancer. Cancer Res. 1988; 48(22): 6587-6592.
28. Price GS, Page RL, Riviere JE, Cline JM, Thrall DE. Pharmacokinetics and toxicity of oral and intravenous lonidamine in dogs. Cancer Chemother. Pharmacol. 1996; 38(2): 129-135.
29. DeAngelis LM, Currie VE, Kim JH, Krol G, O'Hehir MA, Farag FM, Young CW, Posner JB. The combined use of radiation therapy and lonidamine in the treatment of brain metastases. J. Neurooncol 1989; 7(3): 241-247.
30. Weinerman BH, Eisenhauer EA, Besner JG, Coppin CM, Stewart D, Band PR. Phase II study of lonidamine in patients with metastatic renal cell carcinoma: a National Cancer Institute of Canada Clinical Trials Group Study. Cancer Treat. Rep. 1986; 70(6): 751-754.
31. Young CW, Currie VE, Kim JH, Ohehir MA, Farag FM, Kinahan JE. Phase-I and clinical pharmacologic evaluation of lonidamine in patients with advanced cancer. Oncology 1984; 41: 60-65.
32. Mansi JL, Degraeff A, Newell DR, Glaholm J, Button D, Leach MO, Payne G, Smith IE. A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer. Br. J. Cancer 1991; 64(3): 593-597.
33. Di Cosimo S, Ferretti G, Papaldo P, Carlini P, Fabi A, Cognetti F. Lonidamine: efficacy and safety in clinical trials for the treatment of solid tumors. Drugs Today 2003; 39(3): 157-173.
34. Halestrap AP. The monocarboxylate transporter family - structure and functional characterization. IUBMB Life 2012; 64(1): 1-9.
35. Staruch RM, Ganguly M, Tannock IF, Hynynen K, Chopra R. Enhanced drug delivery in rabbit VX2 tumours using thermosensitive liposomes and MRI-controlled focused ultrasound hyperthermia. Int. J. Hyperth. 2012; 28(8): 776-787.
36. Hong CW, Libutti SK, Wood BJ. Liposomal doxorubicin plus radiofrequency ablation for complete necrosis of a hepatocellular carcinoma. Curr. Oncol. 2013; 20(3): E274-E277.
37. Kim JH, Alfieri A, Kim SH, Young CW, Silvestrini B. Radiosensitization of Meth-A fibrosarcoma in mice by lonidamine. Oncology 1984; 41: 36-38.
38. Kim JH, Kim SH, He SQ, Alfieri AA, Young CW. Potentiation of radiation effects on multicellular tumor spheroids (MTS) of HeLa cells by lonidamine. Int. J. Radiat. Oncol. Biol. Phys. 1989; 16(5): 1277-1280.
39. 31P NMR study. Int. J. Hyperth. 2004; 20(4): 335-357.
40. 31P MR spectroscopy study. Radiat. Res. 2005; 164(1): 86-99.
41. Fraker DL, Alexander HR, Andrich M, Rosenberg SA. Treatment of patients with melanoma of the extremity using hyperthermic isolated limb perfusion with melphalan, tumor necrosis factor, and interferon gamma: results of a tumor necrosis factor dose-escalation study. J. Clin. Oncol. 1996; 14(2): 479-489.
42. Canter RJ, Zhou R, Kesmodel SB, Zhang YW, Heitjan DF, Glickson JD, Leeper DB, Fraker DL. Metaiodobenzylguanidine and hyperglycemia augment tumor response to isolated limb perfusion in a rodent model of human melanoma. Ann. Surg. Oncol. 2004; 11(3): 265-273.
43. 31P magnetic resonance spectroscopy study. Cancer Res. 2000; 60(13): 3532-3536.
44. Montanari M, Fabbri F, Rondini E, Frassineti GL, Mattioli R, Carloni S, Scarpi E, Zoli W, Amadori D, Cruciani G. Phase II trial of non-pegylated liposomal doxorubicin and low-dose prednisone in second-line chemotherapy for hormone-refractory prostate cancer. Tumori 2012; 98(6): 696-701.
45. Li N, Zhang CX, Wang XX, Zhang L, Ma X, Zhou J, Ju RJ, Li XY, Zhao WY, Lu WL. Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways. Biomaterials 2013; 34(13): 3366-3380.
46. Solin LJ, Orel SG, Hwang WT, Harris EE, Schnall MD. Relationship of breast magnetic resonance imaging to outcome after breast-conservation treatment with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ. J. Clin. Oncol. 2008; 26(3): 386-391.
47. Gerweck LE, Vijayappa S, Kozin S. Tumor pH controls the in vivo efficacy of weak acid and base chemotherapeutics. Mol. Cancer Ther. 2006; 5(5): 1275-1279.