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Chemical Compound Review

Lonidamin     1-[(2,4-dichlorophenyl) methyl]indazole-3...

Synonyms: Doridamina, Lonidamina, lonidamine, Lonidaminum, DICA, ...
 
 
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Disease relevance of Diclondazolic acid

  • CONCLUSION: The combination of lonidamine and diazepam--drugs that target two distinct mitochondrial sites involved in cellular energy metabolism--potentiates the effects of the individual drugs and may prove useful in the treatment of human glioblastomas [1].
  • However, the inhibitors did not increase the toxicity of the mitochondria-targeting drug lonidamine, and the DNA-specific drugs camptothecin and cisplatin, when used under similar experimental conditions as As2O3 [2].
  • Phase I trial of lonidamine with whole body hyperthermia in advanced cancer [3].
  • PURPOSE: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer [4].
  • Most importantly, ANT2, but not ANT1, silencing facilitated MMP induction by lonidamine, a mitochondrion-targeted antitumor compound already used in clinical studies for breast, ovarian, glioma, and lung cancer as well as prostate adenoma [5].
 

High impact information on Diclondazolic acid

  • However, an increasing number of experimental anticancer drugs, including lonidamine, arsenite, betulinic acid, CD437, and several amphipathic cationic alpha-helical peptides, act directly on mitochondrial membranes and/or on the PTPC [6].
  • We sought to inhibit glioblastoma metabolism by simultaneously inhibiting hexokinase with lonidamine and binding benzodiazepine receptors with diazepam [1].
  • In vivo, the combination of lonidamine and diazepam was significantly more effective in reducing glioblastoma tumor growth than either drug alone (two-sided P<.01, Mann-Whitney U test, comparing growth of treated tumors with that of untreated tumors); this tumor growth retardation was maintained as long as treatment was given [1].
  • We find that apoptosis by lonidamine is independent of the p53 gene [7].
  • The evaluation of bcl-2 protein expression suggests that this different effect of lonidamine treatment in drug-resistant and -sensitive cell lines might not simply be due to dissimilar expression levels of bcl-2 protein [7].
 

Chemical compound and disease context of Diclondazolic acid

 

Biological context of Diclondazolic acid

 

Anatomical context of Diclondazolic acid

 

Associations of Diclondazolic acid with other chemical compounds

  • Interestingly, lonidamine fails to activate the apoptotic program in the corresponding sensitive parental cell lines (ADR-sensitive MCF-7 WT, and nitrosourea-sensitive LI cells) even after long exposure times [7].
  • Patients on arm B received CDDP 80 mg/m2, epirubicin 80 mg/m2, and vindesine 3 mg/m2, all delivered on day 1 every 4 weeks, plus lonidamine orally 150 mg three times daily (54 patients) [15].
  • Lonidamine or exogenous lactate further lowered intracellular pH [16].
  • In the A2780/cp8 cell line, lonidamine was also able to significantly enhance the accumulation of cisplatin-induced DNA interstrand cross-links [17].
  • Etoposide plus lonidamine was significantly more active than etoposide alone only with CTX and BCNU in tumor-cell vs. bone-marrow killing [18].
 

Gene context of Diclondazolic acid

 

Analytical, diagnostic and therapeutic context of Diclondazolic acid

  • Combination therapy: lonidamine, hyperthermia, and chemotherapy against the RIF-1 tumor in vivo [23].
  • The present results of the potentiating effects of radiation may be attributed, in part, to the findings of cell culture studies that lonidamine is a potent inhibitor of repair of potentially lethal damage [12].
  • After 12 hours, the hearts were reperfused for 60 minutes at 37 degrees C with or without perfusing the hearts during first 15 minutes of reperfusion with PTP openers lonidamine (30 microM) or atractyloside (20 microM) [24].
  • CONCLUSION: The addition of lonidamine to hyperfractionated radiotherapy was correlated with a statistically and clinically significant proportion of long-term disease-free patients [25].
  • The reported therapeutic efficacy and the peculiar toxic profile make lonidamine an interesting new drug for future clinical trials [26].

References

  1. Potentiation of lonidamine and diazepam, two agents acting on mitochondria, in human glioblastoma treatment. Miccoli, L., Poirson-Bichat, F., Sureau, F., Bras Gonçalves, R., Bourgeois, Y., Dutrillaux, B., Poupon, M.F., Oudard, S. J. Natl. Cancer Inst. (1998) [Pubmed]
  2. Pharmacologic inhibitors of PI3K/Akt potentiate the apoptotic action of the antileukemic drug arsenic trioxide via glutathione depletion and increased peroxide accumulation in myeloid leukemia cells. Ramos, A.M., Fernández, C., Amrán, D., Sancho, P., de Blas, E., Aller, P. Blood (2005) [Pubmed]
  3. Phase I trial of lonidamine with whole body hyperthermia in advanced cancer. Robins, H.I., Longo, W.L., Lagoni, R.K., Neville, A.J., Hugander, A., Schmitt, C.L., Riggs, C. Cancer Res. (1988) [Pubmed]
  4. Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide. Papaldo, P., Lopez, M., Cortesi, E., Cammilluzzi, E., Antimi, M., Terzoli, E., Lepidini, G., Vici, P., Barone, C., Ferretti, G., Di Cosimo, S., Nistico, C., Carlini, P., Conti, F., Di Lauro, L., Botti, C., Vitucci, C., Fabi, A., Giannarelli, D., Marolla, P. J. Clin. Oncol. (2003) [Pubmed]
  5. Chemosensitization by knockdown of adenine nucleotide translocase-2. Le Bras, M., Borgne-Sanchez, A., Touat, Z., El Dein, O.S., Deniaud, A., Maillier, E., Lecellier, G., Rebouillat, D., Lemaire, C., Kroemer, G., Jacotot, E., Brenner, C. Cancer Res. (2006) [Pubmed]
  6. Mitochondrion as a novel target of anticancer chemotherapy. Costantini, P., Jacotot, E., Decaudin, D., Kroemer, G. J. Natl. Cancer Inst. (2000) [Pubmed]
  7. Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene. Del Bufalo, D., Biroccio, A., Soddu, S., Laudonio, N., D'Angelo, C., Sacchi, A., Zupi, G. J. Clin. Invest. (1996) [Pubmed]
  8. Time to progression in metastatic breast cancer patients treated with epirubicin is not improved by the addition of either cisplatin or lonidamine: final results of a phase III study with a factorial design. Berruti, A., Bitossi, R., Gorzegno, G., Bottini, A., Alquati, P., De Matteis, A., Nuzzo, F., Giardina, G., Danese, S., De Lena, M., Lorusso, V., Farris, A., Sarobba, M.G., DeFabiani, E., Bonazzi, G., Castiglione, F., Bumma, C., Moro, G., Bruzzi, P., Dogliotti, L. J. Clin. Oncol. (2002) [Pubmed]
  9. Effect of lonidamine on the energy metabolism of Ehrlich ascites tumor cells. Floridi, A., Paggi, M.G., D'Atri, S., De Martino, C., Marcante, M.L., Silvestrini, B., Caputo, A. Cancer Res. (1981) [Pubmed]
  10. Lonidamine as a modulator of alkylating agent activity in vitro and in vivo. Teicher, B.A., Herman, T.S., Holden, S.A., Epelbaum, R., Liu, S.D., Frei, E. Cancer Res. (1991) [Pubmed]
  11. Lonidamine, a selective inhibitor of aerobic glycolysis of murine tumor cells. Floridi, A., Paggi, M.G., Marcante, M.L., Silvestrini, B., Caputo, A., De Martino, C. J. Natl. Cancer Inst. (1981) [Pubmed]
  12. Potentiation of radiation effects on two murine tumors by lonidamine. Kim, J.H., Alfieri, A.A., Kim, S.H., Young, C.W. Cancer Res. (1986) [Pubmed]
  13. Testin is tightly associated with testicular cell membrane upon its secretion by sertoli cells whose steady-state mRNA level in the testis correlates with the turnover and integrity of inter-testicular cell junctions. Grima, J., Zhu, L., Cheng, C.Y. J. Biol. Chem. (1997) [Pubmed]
  14. Lonidamine triggers apoptosis via a direct, Bcl-2-inhibited effect on the mitochondrial permeability transition pore. Ravagnan, L., Marzo, I., Costantini, P., Susin, S.A., Zamzami, N., Petit, P.X., Hirsch, F., Goulbern, M., Poupon, M.F., Miccoli, L., Xie, Z., Reed, J.C., Kroemer, G. Oncogene (1999) [Pubmed]
  15. Cisplatin, gemcitabine, and vinorelbine combination therapy in advanced non-small-cell lung cancer: a phase II randomized study of the Southern Italy Cooperative Oncology Group. Comella, P., Frasci, G., Panza, N., Manzione, L., Lorusso, V., Di Rienzo, G., Cioffi, R., De Cataldis, G., Maiorino, L., Bilancia, D., Nicolella, G., Natale, M., Carpagnano, F., Pacilio, C., De Lena, M., Bianco, A., Comella, G. J. Clin. Oncol. (1999) [Pubmed]
  16. The H+-Linked Monocarboxylate Transporter (MCT1/SLC16A1): A Potential Therapeutic Target for High-Risk Neuroblastoma. Fang, J., Quinones, Q.J., Holman, T.L., Morowitz, M.J., Wang, Q., Zhao, H., Sivo, F., Maris, J.M., Wahl, M.L. Mol. Pharmacol. (2006) [Pubmed]
  17. Enhancement of cisplatin activity by lonidamine in human ovarian cancer cells. Silvestrini, R., Zaffaroni, N., Villa, R., Orlandi, L., Costa, A. Int. J. Cancer (1992) [Pubmed]
  18. Etoposide with lonidamine or pentoxifylline as modulators of alkylating agent activity in vivo. Tanaka, J., Teicher, B.A., Herman, T.S., Holden, S.A., Dezube, B., Frei, E. Int. J. Cancer (1991) [Pubmed]
  19. Contribution of caveolin-1 alpha and Akt to TNF-alpha-induced cell death. Ono, K., Iwanaga, Y., Hirayama, M., Kawamura, T., Sowa, N., Hasegawa, K. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  20. Lonidamine as a modulator of taxol activity in human ovarian cancer cells: effects on cell cycle and induction of apoptosis. Orlandi, L., Zaffaroni, N., Bearzatto, A., Villa, R., De Marco, C., Silvestrini, R. Int. J. Cancer (1998) [Pubmed]
  21. Morphological changes in the hearts of CD1 mice following chronic treatment with doxorubicin and lonidamine. Sanguedolce, R., Flandina, C., Cucchiara, T., Varvara, F., Rausa, L. Res. Commun. Chem. Pathol. Pharmacol. (1993) [Pubmed]
  22. Mechanism of lonidamine inhibition of the CFTR chloride channel. Gong, X., Burbridge, S.M., Lewis, A.C., Wong, P.Y., Linsdell, P. Br. J. Pharmacol. (2002) [Pubmed]
  23. Combination therapy: lonidamine, hyperthermia, and chemotherapy against the RIF-1 tumor in vivo. Ning, S.C., Hahn, G.M. Cancer Res. (1991) [Pubmed]
  24. Mitochondrial permeability transition-pore inhibition enhances functional recovery after long-time hypothermic heart preservation. Rajesh, K.G., Sasaguri, S., Ryoko, S., Maeda, H. Transplantation (2003) [Pubmed]
  25. Double-blind randomized study of lonidamine and radiotherapy in head and neck cancer. Magno, L., Terraneo, F., Bertoni, F., Tordiglione, M., Bardelli, D., Rosignoli, M.T., Ciottoli, G.B. Int. J. Radiat. Oncol. Biol. Phys. (1994) [Pubmed]
  26. Toxicity and clinical tolerance of lonidamine. Robustelli della Cuna, G., Pedrazzoli, P. Semin. Oncol. (1991) [Pubmed]
 
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