HU-331: A cannabinoid quinone, with uncommon cytotoxic properties and low toxicity

Expert Opinion on Investigational Drugs

Volumn 16, Issue 9, 2007, Pages 1405-1413

  Peters, Maximilian ^a   Kogan, Natalya M ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

Antiangiogenesis; Apoptosis; Cannabinoid; Cardiotoxicity; Preclinical study; Quinone; Topoisomerase II

Indexed keywords

2,3 BIS(3,5 DIOXO 1 PIPERAZINYL)BUTANE; 2,6 DIOXOPIPERAZINE DERIVATIVE; ANTIOXIDANT; CAMPTOTHECIN; CANNABIS; CREMOPHOR; CYTOTOXIC AGENT; DNA TOPOISOMERASE; DOXORUBICIN; ETOPOSIDE; F 11872; GYRASE INHIBITOR; HU 331; PACLITAXEL; POLYSORBATE 80; QUINONE DERIVATIVE; RAZOXANE; TAFLUPOSIDE; UNCLASSIFIED DRUG; WIN 58161; ANGIOGENESIS INHIBITOR; CANNABIDIOL; CANNABIDIOL HYDROXYQUINONE; CANNABINOID; CYTOTOXIN; DRUG DERIVATIVE;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CACHEXIA; CARDIOTOXICITY; CLINICAL TRIAL; CYTOTOXICITY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG MECHANISM; DRUG MEGADOSE; DRUG STRUCTURE; DRUG SYNTHESIS; ENDOTHELIUM CELL; ENZYME INHIBITION; HUMAN; IN VIVO STUDY; LEUKEMIA; LYMPHOMA; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; METASTASIS; NONHUMAN; OXIDATION; REVIEW; SINGLE DRUG DOSE; UNSPECIFIED SIDE EFFECT; ANIMAL; CELL CULTURE; CELL DEATH; CHEMISTRY; DRUG EFFECT; PHYSIOLOGY;

ANGIOGENESIS INHIBITORS; ANIMALS; CANNABIDIOL; CANNABINOIDS; CELL DEATH; CYTOTOXINS; HUMANS; QUINONES; TUMOR CELLS, CULTURED;

EID: 34548551313     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.16.9.1405     Document Type: Review

References (63)

1. KOGAN NM, RABINOWITZ R, LEVI P et al.: Synthesis and antitumor activity of quinonoid derivatives of cannabinoids. J. Med. Chem. (2004) 47(15):3800-3806.
2. MECHOULAM R, BEN-ZVI Z, GAONI Y: Hashish-XIII: on the nature of the beam test. Tetrahedron (1968) 24(16):5615-5624.
3. KOGAN NM: Cannabinoids and cancer. Mini Rev. Med. Chem. (2005) 5:941-952.
4. MASSI P, VACCANI A, BIANCHESSI S et al.: The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells. Cell Mol. Life Sci. (2006) 63(17):2057-2066.
5. MINOTTI G, MENNA P, SALVATORELLI E, CAIRO G, GIANNI L: Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. (2004) 56(2):185-229.
6. KONSTANTINOPOULOS PA, PAPAVASSILIOU AG: 17-AAG: mechanisms of antitumour activity. Expert Opin. Investig. Drugs (2005) 14(12):1471-1474.
7. UENO T, TAKAHASHI H, ODA M et al.: Inhibition of human telomerase by rubromycins: implication of spiroketal system of the compounds as an active moiety. Biochemistry (2000) 39(20):5995-6002.
8. KOGAN NM, SCHLESINGER M, PRIEL E et al.: HU-331, a novel cannabinoid-based anticancer topoisomerase II inhibitor. Mol. Cancer Ther. (2007) 6(1):173-183.
9. TRAVER RD, HORIKOSHI T, DANENBERG KD et al.: NAD(P)H: quinone oxidoreductase gene expression in human colon carcinoma cells: characterization of a mutation which modulates DT-diaphorase activity and mitomycin sensitivity. Cancer Res. (1992) 52(4):797-802.
10. TSAI-PFLUGFELDER M, LIU LF, LIU AA et al.: Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc. Natl. Acad. Sci. USA (1988) 85(19):7177-7181.
11. AUSTIN CA, SNG J-H, PATEL S, FISHER LM: Novel HeLa topoisomerase II is the IIβ isoform: complete coding sequence and homology with other type II topoisomerases. Biochim. Biophys. Acta 1172(3):283-291.
12. WOESSNER RD, MATTERN MR, MIRABELLI CK, JOHNSON RK, DRAKE FH: Proliferation- and cell cycle-dependent differences in expression of the 170 kilodalton and 180 kilodalton forms of topoisomerase II in NIH-3T3 cells. Cell Growth Differ. (1991) 2(4):209-214.
13. BENDER RP, HAM AJL, OSHEROFF N: Quinone-induced enhancement of DNA cleavage by human topoisomerase IIα: adduction of cysteine residues 392 and 405. Biochemistry (2007) 46(10):2856-2864.
14. LENNERNÃS B, ALBERTSSON P, LENNERNÃS H, NORRBY K: Chemotherapy and antiangiogenesis. Acta Oncol. (2003) 42(4):294-303.
15. FERRARA N, HILLAN KJ, NOVOTNY W: Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem. Biophys. Res. Commun. (2005) 333(2):328-335.
16. KOGAN NM, BLAZQUEZ C, ALVAREZ L et al.: A cannabinoid quinone inhibits angiogenesis by targeting vascular endothelial cells. Mol. Pharmacol. (2006) 70(1):51-59.
17. KOGAN NM, SCHLESINGER M, PETERS M, MARINCHEVA G, BEERI R, MECHOULAM R: A cannabinoid anticancer quinone, HU-331, is more potent and less cardiotoxic than doxorubicin - a comparative in vivo study. J. Pharmacol. Exp. Ther. (2007) 322(2):646-653.
18. SINGLA AK, GARG A, AGGARWAL D: Paclitaxel and its formulations. Int. J. Pharm. (2002) 235(1-2):179-192.
19. TEN TIJE AJ, LOOS WJ, VERWEIJ J et al.: Disposition of polyoxyethylated excipients in humans: implications for drug safety and formulation approaches. Clin. Pharmacol Ther. (2003) 74(5):509-510.
20. BARANCZEWSKI P, STAŃ CZAK A, SUNDBERG K et al.: Introduction to in vitro estimation of metabolic stability and drug interactions of new chemical entities in drug discovery and development. Pharmacol. Rep. (2006) 58(4):453-472.
21. YAN Z, CALDWELL GW: Metabolism profiling, and cytochrome P450 inhibition & induction in drug discovery. Curr. Top. Med. Chem. (2001) 1(5):403-425.
22. BORNHEIM LM, GRILLO MP: Characterization of cytochrome P450 3A inactivation by cannabidiol: possible involvement of cannabidiol-hydroxyquinone as a P450 inactivator. Chem. Res. Toxicol. (1998) 11(10):1209-1216.
23. WATANABE K, USAMI N, YAMAMOTO I, YOSHIMURA H: Inhibitory effect of cannabidiol hydroxy-quinone, and oxidative product of cannabidiol, on the hepatic microsomal drug-metabolizing enzymes of mice. J. Pharmacobiodyn. (1991) 14(7):421-427.
24. HARVEY DJ, SAMARA E, MECHOULAM R: Comparative metabolism of cannabidiol in dog, rat and man. Pharmacol. Biochem. Behav. (1991) 40(3):523-532.
25. GEWIRTZ DA: A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem. Pharmacol. (1999) 57(7):727-741.
26. FORNARI FA, RANDOLPH JK, YALOWICH JC, RITKE MK, GEWIRTZ DA: Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells. Mol. Pharmacol. (1994) 45(4):649-656.
27. DOROSHOW JH, SYNOLD TW, SOMLO G, AKMAN SA, GAJEWSKI E: Oxidative DNA base modifications in peripheral blood mononuclear cells of patients created with high-dose infusional doxorubicin. Blood (2001) 97(9):2839-2845.
28. LUCE RA, SIGURDSSON ST, HOPKINS PB: Quantification of formaldehyde-mediated covalent adducts of adriamycin with DNA. Biochemistry (1999) 38(27):8682-8690.
29. GAJEWSKI E, GAUR S, AKMAN SA et al.: Oxidative DNA base damage in MCF-10A breast epithelial cells at clinically achievable concentrations of doxorubicin. Biochem. Pharmacol. (2007) 73(12):1947-1956.
30. FORNARI FA, JARVIS WD, GRANT S et al.: Growth arrest and non-apoptotic cell death associated with the suppression of c-myc expression in MCF-7 breast rumor cells following acute exposure to doxorubicin. Biochem. Pharmacol. (1996) 51(7):931-940.
31. WENTLAND MP, LESHER GY, REUMAN M et al.: Mammalian topoisomerase II inhibitory activity of 1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(2,6-dimethyl-4-pyridinyl) -4-oxo-3-quinolinecarboxylic acid and related derivatives. J. Med. Chem. (1993) 36(19):2801-2809.
32. COUGHLIN SA, DANZ DW, ROBINSON RG et al.: Mechanism of action and antitumor activity of (S)-10-(2,6-dimethyl-4-pyridinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro- 7H-pyridol [1,2,3-de]-[1,4]benzothiazine-6-carboxylic acid (WIN 58161). Biochem. Pharmacol. (1995) 50(1):111-122.
33. PERRIN D, VAN HILLE B, BARRET J-M et al.: F11782, a novel epipodophylloid non-intercalating dual catalytic inhibitor of topoisomerases I and II with an original mechanism of action. Biochem. Pharmacol. (2000) 59(7):807-819.
34. BARRET JM, HILL BT, OLIVE PL: Characterization of DNA-strand breakage induced in V79 cells by F 11782, a catalytic inhibitor of topoisomerases. Br. J. Cancer (2000) 83(12):1740-1746.
35. BARRET J-M, CADOU M, HILL BT: Inhibition of nucleotide excision repair and sensitisation of cells to DNA cross-linking an anticancer drugs by F 11782, a novel fluorinated epipodophylloid. Biochem. Pharmacol. (2002) 63(2):251-258.
36. KRUCZYNSKI A, RICOME C, WAUD WR, HILL BT: In vivo antitumor activity F 11782, a non-intercalating dual catalytic inhibitor of topoisomerases I and II, against a panel of human rumor xenografts. J. Exp. Ther. Oncol. (2002) 2(4):219-227.
37. KRUCZYNSKI A, ETIEVANT C, PERRIN D et al.: Preclinical antitumour activity of F 11782, a novel dual catalytic inhibitor of topoisomerases. Br. J. Cancer (2000) 83(11):1516-1524.
38. BARRET J-M, KRUCZYNSKI A, ETIÉVANT C, HILL BT. Synergistic effects of F 11782, a novel dual inhibitor of topoisomerases I and II, in combination with other anticancer agents. Cancer Chemother. Pharmacol. (2002) 49(6):479-486.
39. SARGENT JM, ELGIE AW, WILLIAMSON CJ, HILL BT: Ex vivo effects of the dual topoisomerase inhibitor tafluposide (F 11782) on cells isolated from fiesh tumor samples taken from patients with cancer. Anticancer Drugs (2003) 14(6):467-473.
40. CREIGHTON AM, HELLMANN K, WHITECROSS S: Antitumour activity in a series of bis-diketopiperazines. Nature (1969) 222(5191):384-385.
41. MARTY M, ESPIE M, LLOMBART A et al.: Multicenter randomized Phase III study of the cardioprotective effect of dexrazoxane (Cardioxane®) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy. Ann. Oncol. (2006) 17(4):614-622.
42. HASINOFF BB, KUSCHAK TI, YALOWICH JC, CREIGHTON AM: A QSAR study comparing the cytotoxicity and DNA topoisomerase II inhibitory effects of bis-dioxopiperazine analogs of ICRF-187 (dexrazoxane). Biochem. Pharmacol. (1995) 50(7):953-958.
43. TANABE K, IKEGAMI Y, ISHIDA R, ANDOH T: Inhibition of topoisomerase II by antitumor agents bis(2,6-dioxopiperazine) derivatives. Cancer Res. (1991) 51(18):4903-4908.
44. ROCA J, ISHIDA R, BERGER JM, ANDOH T, WANG JC: Antitumor bis-dioxopiperazines inhibit yeast DNA topoisomerase II by trapping the enzyme in the form of a closed protein clamp. Proc. Natl. Acad. Sci. USA (1994) 91(5):1781-1785.
45. HOLM C, GOTO T, WANG JC, BOTSTEIN D: DNA topoisomerase II is required at the time of mitosis in yeast. Cell(1985) 41(2):553-563.
46. SKOUFIAS DA, LACROIX FB, ANDREASSEN PR, WILSON L, MARGOLIS RL: Inhibition of DNA decatenation, but not DNA damage, arrests cells at metaphase. Mol. Cell (2004) 15(6):977-990.
47. HOSSAIN MS, AKIMITSU N, TAKAKI T, HIRAI H, SEKIMIZU K: ICRF-193, a catalytic inhibitor of DNA topoisomerase II, inhibits re-entry into the cell division cycle from quiescent state in mammalian cells. Genes Cells (2002) 7(3):285-294.
48. HAJJI N, PASTOR N, MATEOS S, DOMINGUEZ I, CORTES F: DNA strand breaks induced by the anti-topoisomerase II bis-dioxopiperazine ICRF-193. Mutat. Res. (2003) 530(1-2):35-46.
49. VAN HILLE B, ETIÉVANT C, BARRET J-M, KRUCZYNSKI A, HILL BT: Characterization of the biological and biochemical activities of F 11782 and the bis-dioxopiperazines, ICRF-187 and ICRF-193, two types of topoisomerase II catalytic inhibitors with distinctive mechanisms of action. Anticancer Drugs (2000) 11(10):829-841.
50. BASU AK, MARNETT LJ: Unequivocal demonstration that malondialdehyde is a mutagen. Carcinegenesis (1983) 4(3):331-333.
51. HANDE KR: Clinical applications of anticancer drugs targeted to topoisomerase II. Biochim. Biophys. Acta (1998) 1400(1-3):173-184.
52. FAN E, SHI W, LOWARY TL: Synthesis of daunorubicin analogues containing truncated aromatic cores and unnatural monosaccharide residues. J. Org. Chem. (2007) 72(8):2917-2928.
53. MANFREDINI S, BAZZANINI R, BARALDI PG et al.: Design, synthesis and antiproliferative activity of methyl 4-iodo-1-β-D-ribofuranosyl-pyrazole-3-carboxylate and related compounds. Bioorg. Med. Chem. Lett. (1996) 6(11):1279-1284.
54. SERPE L, CATALANO MG, CAVALLI R et al.: Cytotoxicity of anticancer drugs incorporated in solid lipid nanoparticles on HT-29 colorectal cancer cell line. Eur. J. Pharm. Biopharm. (2004) 58(3):673-680.
55. RHEE H-K, PARK HJ, LEE SK, LEE C-O, CHOO H-YP: Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones. Bioorg. Med. Chem. (2007) 15(4):1651-1658.
56. KIM S, SUNG M, KANG K et al.: DA-125, a novel anthracycline derivative showing high-affinity DNA binding and topoisomerase II inhibitory activities, exerts cytotoxicity via c-Jun N-terminal kinase pathway. Cancer Chemother. Pharmacol. (2001) 47(6):511-518.
57. BROKER LE, KRUYT FA, GIACCONE G: Cell death independent of caspases: a review. Clin. Cancer Res. (2005) 11(9):3155-3162.
58. OKADA H, MAK TW: Pathways of apoptotic and non-apoptotic death in tumour cells. Nat. Rev. Cancer (2004) 4(8):592-603.
59. SPERANDIO S, POKSAY K, DE BELLE I et al.: Paraptosis: mediation by MAP kinases and inhibition by AIP-1/Alix. Cell Death Differ. (2004) 11(10):1066-1075.
60. BAEHRECKE EH: Autophagy: dual roles in life and death? Nat. Rev. Mol. Cell Biol. (2005) 6(6):505-510.
61. FESTJENS N, VANDEN BERGHE T, VANDENABEELE P: Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim. Biophys. Acta (2006) 1757(9-10):1371-1387.
62. ZONG WX, DITSWORTH D, BAUER DE, WANG ZQ, THOMPSON CB: Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev. (2004) 18(11):1272-1282.
63. LI YZ, LI CJ, PINTO AV, PARDEE AB: Release of mitochondrial cytochrome C in both apoptosis and necrosis induced by β-lapachone in human carcinoma cells. Mol. Med. (1999) 5(4):232-239.