Mechanistic insights into the antileukemic activity of hyperforin

Current Cancer Drug Targets

Volumn 13, Issue 1, 2013, Pages 1-10

  Billard, C ^a,b   Merhi, F ^a,b   Bauvois, B ^a,b  

^a CENTRE DE RECHERCHE DES CORDELIERS   (France)

^b SORBONNE UNIVERSITÉ   (France)

Author keywords

Apoptosis; Drug resistance; Hyperforin; Leukemia; Proliferation; Signaling

Indexed keywords

ABC TRANSPORTER; APOPTOTIC PROTEASE ACTIVATING FACTOR 1; ARISTOFORIN; BORTEZOMIB; CYCLOSPORIN; CYTOCHROME P450 1A1; CYTOCHROME P450 3A4; GELATINASE A; GELATINASE B; HYPERFORIN; HYPERICUM PERFORATUM EXTRACT; MULTIDRUG RESISTANCE PROTEIN 1; PHLOROGLUCINOL; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN KINASE B; PROTEIN MCL 1; PROTEIN NOXA; UNCLASSIFIED DRUG; VASCULOTROPIN;

ACUTE GRANULOCYTIC LEUKEMIA; ANGIOGENESIS; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL (TOPIC); DOWN REGULATION; DRUG MEGADOSE; HUMAN; INFLAMMATION; LEUKEMIA; LEUKOCYTE; LOW DRUG DOSE; LYMPHANGIOGENESIS; NEOPLASM; NONHUMAN; PHOSPHORYLATION; REVIEW;

EID: 84874640152     PISSN: 15680096     EISSN: 18735576     Source Type: Journal    
DOI: 10.2174/156800913804486601     Document Type: Review

References (123)

1. Clement, K.; Covertson, C. R.; Johnson, M. J.; Dearing, K. St. John's wort and the treatment of mild to moderate depression: a systematic review. Holist. Nurs. Pract. 2006, 20, 197-203.
2. Medina, M. A.; Martinez-Poveda, B.; Amores-Sanchez, M. I.; Quesada, A. R. Hyperforin: more than an antidepressant bioactive compound? Life Sci. 2006, 79, 105-111.
3. Quiney, C.; Billard, C.; Salanoubat, C.; Fourneron, J. D.; Kolb, J. P. Hyperforin, a new lead compound against the progression of cancer and leukemia? Leukemia 2006, 20, 1519-1525.
4. Linde, K.; Berner, M. M.; Kriston, L. St John's wort for major depression. Cochrane Database Syst. Rev. 2008, CD000448.
5. Smelcerovic, A.; Spiteller, M.; Zuehlke, S. Comparison of methods for the exhaustive extraction of hypericins, flavonoids, and hyperforin from Hypericum perforatum L. J. Agric. Food Chem. 2006, 54, 2750-2753.
6. Butterweck, V.; Schmidt, M. St. John's wort: role of active compounds for its mechanism of action and efficacy. Wien Med. Wochenschr. 2007, 157, 356-361.
7. Tatsis, E. C.; Boeren, S.; Exarchou, V.; Troganis, A. N.; Vervoort, J.; Gerothanassis, I. P. Identification of the major constituents of Hypericum perforatum by LC/SPE/NMR and/or LC/MS. Phytochemistry 2007, 68, 383-393.
8. Saddiqe, Z.; Naeem, I.; Maimoona, A. A review of the antibacterial activity of Hypericum perforatum L. J. Ethnopharmacol. 2010, 131, 511-521.
9. Muller, W. E.; Singer, A.; Wonnemann, M. Hyperforin-antidepressant activity by a novel mechanism of action. Pharmacopsychiatry 2001, 34 (Suppl 1), S98-102.
10. Zanoli, P. Role of hyperforin in the pharmacological activities of St. John's Wort. CNS Drug Rev. 2004, 10, 203-218.
11. Bischoff, S. C. Quercetin: potentials in the prevention and therapy of disease. Curr. Opin. Clin. Nutr. Metab. Care 2008, 11, 733-740.
12. Karioti, A.; Vincieri, F. F.; Bilia, A. R. Rapid and efficient purification of naphthodianthrones from St. John's wort extract by using liquid-liquid extraction and SEC. J. Sep. Sci. 2009, 32, 1374-1382.
13. Chirumbolo, S. The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm. Allergy Drug Targets 2010, 9, 263-285.
14. Nahrstedt, A.; Butterweck, V. Lessons learned from herbal medicinal products: the example of St. John's Wort. J. Nat. Prod. 2010, 73, 1015-1021.
15. Vasanthi, H. R.; Shrishrimal, N.; Das, D. K. Phytochemicals from plants to combat cardiovascular disease. Curr. Med. Chem. 2012, 19, 2242-2251.
16. Weng, C. J.; Yen, G. C. Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo antimetastatic activities. Cancer Metastasis Rev. 2012, 31, 323-351.
17. Adam, P.; Arigoni, D.; Bacher, A.; Eisenreich, W. Biosynthesis of hyperforin in Hypericum perforatum. J. Med. Chem. 2002, 45, 4786-4793.
18. Boubakir, Z.; Beuerle, T.; Liu, B.; Beerhues, L. The first prenylation step in hyperforin biosynthesis. Phytochemistry 2005, 66, 51-57.
19. Beerhues, L. Hyperforin. Phytochemistry 2006, 67, 2201-2207.
20. Griffith, T. N.; Varela-Nallar, L.; Dinamarca, M. C.; Inestrosa, N. C. Neurobiological effects of Hyperforin and its potential in Alzheimer's disease therapy. Curr. Med. Chem. 2010, 17, 391-406.
21. Schempp, C. M.; Kirkin, V.; Simon-Haarhaus, B.; Kersten, A.; Kiss, J.; Termeer, C. C.; Gilb, B.; Kaufmann, T.; Borner, C.; Sleeman, J. P.; Simon, J. C. Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis. Oncogene 2002, 21, 1242-1250.
22. Dona, M.; Dell'Aica, I.; Pezzato, E.; Sartor, L.; Calabrese, F.; Della Barbera, M.; Donella-Deana, A.; Appendino, G.; Borsarini, A.; Caniato, R.; Garbisa, S. Hyperforin inhibits cancer invasion and metastasis. Cancer Res. 2004, 64, 6225-6232.
23. Martinez-Poveda, B.; Quesada, A. R.; Medina, M. A. Hyperforin, a bio-active compound of St. John's Wort, is a new inhibitor of angiogenesis targeting several key steps of the process. Int. J. Cancer 2005, 117, 775-780.
24. Lorusso, G.; Vannini, N.; Sogno, I.; Generoso, L.; Garbisa, S.; Noonan, D. M.; Albini, A. Mechanisms of Hyperforin as an antiangiogenic angioprevention agent. Eur. J. Cancer 2009, 45, 1474-1484.
25. Schempp, C. M.; Kiss, J.; Kirkin, V.; Averbeck, M.; Simon-Haarhaus, B.; Kremer, B.; Termeer, C. C.; Sleeman, J.; Simon, J. C. Hyperforin acts as an angiogenesis inhibitor. Planta Med. 2005, 71, 999-1004.
26. Zhou, C.; Tabb, M. M.; Sadatrafiei, A.; Grun, F.; Sun, A.; Blumberg, B. Hyperforin, the active component of St. John's wort, induces IL-8 expression in human intestinal epithelial cells via a MAPK-dependent, NF-kappaB-independent pathway. J. Clin. Immunol. 2004, 24, 623-636.
27. Whitten, D. L.; Myers, S. P.; Hawrelak, J. A.; Wohlmuth, H. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br. J. Clin. Pharmacol. 2006, 62, 512-526.
28. Chen, Y.; Goldstein, J. A. The transcriptional regulation of the human CYP2C genes. Curr. Drug Metab. 2009, 10, 567-578.
29. Tian, R.; Koyabu, N.; Morimoto, S.; Shoyama, Y.; Ohtani, H.; Sawada, Y. Functional induction and de-induction of Pglycoprotein by St. John's wort and its ingredients in a human colon adenocarcinoma cell line. Drug Metab. Dispos. 2005, 33, 547-554.
30. Abuznait, A. H.; Patrick, S. G.; Kaddoumi, A. Exposure of LS-180 cells to drugs of diverse physicochemical and therapeutic properties up-regulates P-glycoprotein expression and activity. J. Pharm. Pharm. Sci. 2011, 14, 236-248.
31. Gutmann, H.; Poller, B.; Buter, K. B.; Pfrunder, A.; Schaffner, W.; Drewe, J. Hypericum perforatum: which constituents may induce intestinal MDR1 and CYP3A4 mRNA expression? Planta Med. 2006, 72, 685-690.
32. Rund, D. Hyperforin modulation of drug resistance: saint or sinner? Leuk. Lymphoma 2007, 48, 1470-1471.
33. Chen, Y.; Ferguson, S. S.; Negishi, M.; Goldstein, J. A. Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor. J. Pharmacol. Exp. Ther. 2004, 308, 495-501.
34. Patel, J.; Buddha, B.; Dey, S.; Pal, D.; Mitra, A. K. In vitro interaction of the HIV protease inhibitor ritonavir with herbal constituents: changes in P-gp and CYP3A4 activity. Am. J. Ther. 2004, 11, 262-277.
35. Lee, J. Y.; Duke, R. K.; Tran, V. H.; Hook, J. M.; Duke, C. C. Hyperforin and its analogues inhibit CYP3A4 enzyme activity. Phytochemistry 2006, 67, 2550-2560.
36. Schwarz, D.; Kisselev, P.; Roots, I. St. John's wort extracts and some of their constituents potently inhibit ultimate carcinogen formation from benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1. Cancer Res. 2003, 63, 8062-8068.
37. Schempp, C. M.; Winghofer, B.; Ludtke, R.; Simon-Haarhaus, B.; Schopf, E.; Simon, J. C. Topical application of St John's wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells. Br. J. Dermatol. 2000, 142, 979-984.
38. Cabrelle, A.; Dell'Aica, I.; Melchiori, L.; Carraro, S.; Brunetta, E.; Niero, R.; Scquizzato, E.; D'Intino, G.; Calza, L.; Garbisa, S.; Agostini, C. Hyperforin down-regulates effector function of activated T lymphocytes and shows efficacy against Th1-triggered CNS inflammatory-demyelinating disease. J. Leukoc. Biol. 2008, 83, 212-219.
39. Feisst, C.; Werz, O. Suppression of receptor-mediated Ca2+ mobilization and functional leukocyte responses by hyperforin. Biochem. Pharmacol. 2004, 67, 1531-1539.
40. Albert, D.; Zundorf, I.; Dingermann, T.; Muller, W. E.; Steinhilber, D.; Werz, O. Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. Biochem. Pharmacol. 2002, 64, 1767-1775.
41. Hammer, K. D.; Hillwig, M. L.; Solco, A. K.; Dixon, P. M.; Delate, K.; Murphy, P. A.; Wurtele, E. S.; Birt, D. F. Inhibition of prostaglandin E(2) production by anti-inflammatory hypericum perforatum extracts and constituents in RAW264.7 mouse macrophage cells. J. Agric. Food Chem. 2007, 55, 7323-7331.
42. Koeberle, A.; Rossi, A.; Bauer, J.; Dehm, F.; Verotta, L.; Northoff, H.; Sautebin, L.; Werz, O. Hyperforin, an anti-inflammatory constituent from St. John's Wort, inhibits microsomal prostaglandin E(2) synthase-1 and suppresses prostaglandin E(2) formation in vivo. Front. Pharmacol. 2011, 2, 7.
43. Dell'Aica, I.; Caniato, R.; Biggin, S.; Garbisa, S. Matrix proteases, green tea, and St. John's wort: biomedical research catches up with folk medicine. Clin. Chim. Acta 2007, 381, 69-77.
44. Schulz, H. U.; Schurer, M.; Bassler, D.; Weiser, D. Investigation of pharmacokinetic data of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin revealed from single and multiple oral dose studies with a hypericum extract containing tablet in healthy male volunteers. Arzneimittelforschung 2005, 55, 561-568.
45. Wurglics, M.; Schubert-Zsilavecz, M. Hypericum perforatum: a 'modern' herbal antidepressant: pharmacokinetics of active ingredients. Clin. Pharmacokinet. 2006, 45, 449-468.
46. Meinke, M. C.; Schanzer, S.; Haag, S. F.; Casetti, F.; Muller, M. L.; Wolfle, U.; Kleemann, A.; Lademann, J.; Schempp, C. M. In vivo photoprotective and anti-inflammatory effect of hyperforin is associated with high antioxidant activity in vitro and ex vivo. Eur. J. Pharm. Biopharm. 2012, 81, 346-350.
47. Mai, I.; Bauer, S.; Perloff, E. S.; Johne, A.; Uehleke, B.; Frank, B.; Budde, K.; Roots, I. Hyperforin content determines the magnitude of the St John's wort-cyclosporine drug interaction. Clin. Pharmacol. Ther. 2004, 76, 330-340.
48. Buchholzer, M. L.; Dvorak, C.; Chatterjee, S. S.; Klein, J. Dual modulation of striatal acetylcholine release by hyperforin, a constituent of St. John's wort. J. Pharmacol. Exp. Ther. 2002, 301, 714-719.
49. Eckert, G. P.; Keller, J. H.; Jourdan, C.; Karas, M.; Volmer, D. A.; Schubert-Zsilavecz, M.; Muller, W. E. Hyperforin modifies neuronal membrane properties in vivo. Neurosci. Lett. 2004, 367, 139-143.
50. Dell'Aica, I.; Niero, R.; Piazza, F.; Cabrelle, A.; Sartor, L.; Colalto, C.; Brunetta, E.; Lorusso, G.; Benelli, R.; Albini, A.; Calabrese, F.; Agostini, C.; Garbisa, S. Hyperforin blocks neutrophil activation of matrix metalloproteinase-9, motility and recruitment, and restrains inflammation-triggered angiogenesis and lung fibrosis. J. Pharmacol. Exp. Ther. 2007, 321, 492-500.
51. Gartner, M.; Muller, T.; Simon, J. C.; Giannis, A.; Sleeman, J. P. Aristoforin, a novel stable derivative of hyperforin, is a potent anticancer agent. Chembiochem. 2005, 6, 171-177.
52. Sosa, S.; Pace, R.; Bornancin, A.; Morazzoni, P.; Riva, A.; Tubaro, A.; Della Loggia, R. Topical anti-inflammatory activity of extracts and compounds from Hypericum perforatum L. J. Pharm. Pharmacol. 2007, 59, 703-709.
53. Rothley, M.; Schmid, A.; Thiele, W.; Schacht, V.; Plaumann, D.; Gartner, M.; Yektaoglu, A.; Bruyere, F.; Noel, A.; Giannis, A.; Sleeman, J. P. Hyperforin and aristoforin inhibit lymphatic endothelial cell proliferation in vitro and suppress tumor-induced lymphangiogenesis in vivo. Int. J. Cancer 2009, 125, 34-42.
54. Feisst, C.; Pergola, C.; Rakonjac, M.; Rossi, A.; Koeberle, A.; Dodt, G.; Hoffmann, M.; Hoernig, C.; Fischer, L.; Steinhilber, D.; Franke, L.; Schneider, G.; Rådmark, O.; Sautebin, L.; Werz, O. Hyperforin is a novel type of 5-lipoxygenase inhibitor with high efficacy in vivo. Cell Mol. Life Sci. 2009, 66, 2759-2771.
55. Kolb, J. P.; Kern, C.; Quiney, C.; Roman, V.; Billard, C. Reestablishment of a normal apoptotic process as a therapeutic approach in B-CLL. Curr. Drug Targets Cardiovasc. Haematol. Disord. 2003, 3, 261-286.
56. Pleyer, L.; Egle, A.; Hartmann, T. N.; Greil, R. Molecular and cellular mechanisms of CLL: novel therapeutic approaches. Nat. Rev. Clin. Oncol. 2009, 6, 405-418.
57. Dighiero, G.; Hamblin, T. J. Chronic lymphocytic leukaemia. Lancet 2008, 371, 1017-1029.
58. Tam, C. S.; Keating, M. J. Chemoimmunotherapy of chronic lymphocytic leukemia. Nat. Rev. Clin. Oncol. 2010, 7, 521-532.
59. Mason, K. D.; Juneja, S. K.; Szer, J. The immunophenotype of acute myeloid leukemia: is there a relationship with prognosis? Blood Rev. 2006, 20, 71-82.
60. King, M. E.; Rowe, J. M. Recent developments in acute myelogenous leukemia therapy. Oncologist 2007, 12 (Suppl 2), 14-21.
61. Plesa, C.; Chelghoum, Y.; Plesa, A.; Elhamri, M.; Tigaud, I.; Michallet, M.; Dumontet, C.; Thomas, X. Prognostic value of immunophenotyping in elderly patients with acute myeloid leukemia: a single-institution experience. Cancer 2008, 112, 572-580.
62. Adams, J. M.; Cory, S. Bcl-2-regulated apoptosis: mechanism and therapeutic potential. Curr. Opin. Immunol. 2007, 19, 488-496.
63. Ledgerwood, E. C.; Morison, I. M. Targeting the apoptosome for cancer therapy. Clin. Cancer Res. 2009, 15, 420-424.
64. Kitada, S.; Andersen, J.; Akar, S.; Zapata, J. M.; Takayama, S.; Krajewski, S.; Wang, H. G.; Zhang, X.; Bullrich, F.; Croce, C. M.; Rai, K.; Hines, J.; Reed, J. C. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with In vitro and In vivo chemoresponses. Blood 1998, 91, 3379-3389.
65. Moon, E. Y.; Lerner, A. PDE4 inhibitors activate a mitochondrial apoptotic pathway in chronic lymphocytic leukemia cells that is regulated by protein phosphatase 2A. Blood 2003, 101, 4122-4130.
66. Sanz, L.; Garcia-Marco, J. A.; Casanova, B.; de La Fuente, M. T.; Garcia-Gila, M.; Garcia-Pardo, A.; Silva, A. Bcl-2 family gene modulation during spontaneous apoptosis of B-chronic lymphocytic leukemia cells. Biochem. Biophys. Res. Commun. 2004, 315, 562-567.
67. Quiney, C.; Billard, C.; Faussat, A. M.; Salanoubat, C.; Ensaf, A.; Nait-Si, Y.; Fourneron, J. D.; Kolb, J. P. Pro-apoptotic properties of hyperforin in leukemic cells from patients with B-cell chronic lymphocytic leukemia. Leukemia 2006, 20, 491-497.
68. Zhao, H.; Dugas, N.; Mathiot, C.; Delmer, A.; Dugas, B.; Sigaux, F.; Kolb, J. P. B-cell chronic lymphocytic leukemia cells express a functional inducible nitric oxide synthase displaying anti-apoptotic activity. Blood 1998, 92, 1031-1043.
69. Dimmeler, S.; Haendeler, J.; Nehls, M.; Zeiher, A. M. Suppression of apoptosis by nitric oxide via inhibition of interleukin-1betaconverting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases. J. Exp. Med. 1997, 185, 601-607.
70. Lin, T. S.; Porcu, P. Flavopiridol: where do we stand in chronic lymphocytic leukemia? Leukemia 2004, 18, 243-246.
71. Smit, L. A.; Hallaert, D. Y.; Spijker, R.; de Goeij, B.; Jaspers, A.; Kater, A. P.; van Oers, M. H.; van Noesel, C. J.; Eldering, E. Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity. Blood 2007, 109, 1660-1668.
72. Zaher, M.; Akrout, I.; Mirshahi, M.; Kolb, J. P.; Billard, C. Noxa upregulation is associated with apoptosis of chronic lymphocytic leukemia cells induced by hyperforin but not flavopiridol. Leukemia 2009, 23, 594-596.
73. Zaher, M.; Tang, R.; Bombarda, I.; Merhi, F.; Bauvois, B.; Billard, C. Mechanism of the pro-apoptotic effect of hyperforin on chronic lymphocytic leukemia cells: upregulation of the BH3-only protein noxa displaces Mcl-1/Bak interaction. Int. J. Oncol. 2011.
74. Ping Dou, Q. Targeting tumor ubiquitin-proteasome pathway with new and old drugs. Curr. Cancer Drug Targets 2011, 11, 236-238.
75. Hostanska, K.; Reichling, J.; Bommer, S.; Weber, M.; Saller, R. Hyperforin a constituent of St John's wort (Hypericum perforatum L.) extract induces apoptosis by triggering activation of caspases and with hypericin synergistically exerts cytotoxicity towards human malignant cell lines. Eur. J. Pharm. Biopharm. 2003, 56, 121-132.
76. Merhi, F.; Tang, R.; Piedfer, M.; Mathieu, J.; Bombarda, I.; Zaher, M.; Kolb, J. P.; Billard, C.; Bauvois, B. Hyperforin inhibits Akt1 kinase activity and promotes caspase-mediated apoptosis involving bad and noxa activation in human myeloid tumor cells. Plos ONE 2011, 6, e25963.
77. Liu, J. Y.; Liu, Z.; Wang, D. M.; Li, M. M.; Wang, S. X.; Wang, R.; Chen, J. P.; Wang, Y. F.; Yang, D. P. Induction of apoptosis in K562 cells by dicyclohexylammonium salt of hyperforin through a mitochondrial-related pathway. Chem. Biol. Interact. 2011, 190, 91-101.
78. Benbrook, D. M.; Masamha, C. P. The pro-survival function of Akt kinase can be overridden or altered to contribute to induction of apoptosis. Curr. Cancer Drug Targets 2011, 11, 586-599.
79. Martelli, A. M.; Nyakern, M.; Tabellini, G.; Bortul, R.; Tazzari, P. L.; Evangelisti, C.; Cocco, L. Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia 2006, 20, 911-928.
80. Datta, S. R.; Brunet, A.; Greenberg, M. E. Cellular survival: a play in three Akts. Genes Dev. 1999, 13, 2905-2927.
81. Bremer, E.; van Dam, G.; Kroesen, B. J.; de Leij, L.; Helfrich, W. Targeted induction of apoptosis for cancer therapy: current progress and prospects. Trends Mol. Med. 2006, 12, 382-393.
82. Klein, T.; Bischoff, R. Physiology and pathophysiology of matrix metalloproteases. Amino Acids 2011, 41, 271-290.
83. Kessenbrock, K.; Plaks, V.; Werb, Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010, 141, 52-67.
84. Bjorklund, M.; Koivunen, E. Gelatinase-mediated migration and invasion of cancer cells. Biochim. Biophys. Acta 2005, 1755, 37-69.
85. Klein, G.; Vellenga, E.; Fraaije, M. W.; Kamps, W. A.; de Bont, E. S. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit. Rev. Oncol. Hematol. 2004, 50, 87-100.
86. Bauvois, B. New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: outside-in signaling and relationship to tumor progression. Biochim. Biophys. Acta-Reviews on Cancer 2012, 1825, 29-36.
87. Aguayo, A.; Kantarjian, H.; Manshouri, T.; Gidel, C.; Estey, E.; Thomas, D.; Koller, C.; Estrov, Z.; O'Brien, S.; Keating, M.; Freireich, E.; Albitar, M. Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood 2000, 96, 2240-2245.
88. Bauvois, B.; Dumont, J.; Mathiot, C.; Kolb, J. P. Production of matrix metalloproteinase-9 in early stage B-CLL: suppression by interferons. Leukemia 2002, 16, 791-798.
89. Kamiguti, A. S.; Lee, E. S.; Till, K. J.; Harris, R. J.; Glenn, M. A.; Lin, K.; Chen, H. J.; Zuzel, M.; Cawley, J. C. The role of matrix metalloproteinase 9 in the pathogenesis of chronic lymphocytic leukaemia. Br. J. Haematol. 2004, 125, 128-140.
90. Redondo-Munoz, J.; Escobar-Diaz, E.; Samaniego, R.; Terol, M. J.; Garcia-Marco, J. A.; Garcia-Pardo, A. MMP-9 in B-cell chronic lymphocytic leukemia is up-regulated by alpha4beta1 integrin or CXCR4 engagement via distinct signaling pathways, localizes to podosomes, and is involved in cell invasion and migration. Blood 2006, 108, 3143-3151.
91. Redondo-Munoz, J.; Ugarte-Berzal, E.; Terol, M. J.; Van den Steen, P. E.; Hernandez del Cerro, M.; Roderfeld, M.; Roeb, E.; Opdenakker, G.; Garcia-Marco, J. A.; Garcia-Pardo, A. Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia b cell survival through its hemopexin domain. Cancer Cell 2010, 17, 160-172.
92. Quiney, C.; Billard, C.; Mirshahi, P.; Fourneron, J. D.; Kolb, J. P. Hyperforin inhibits MMP-9 secretion by B-CLL cells and microtubule formation by endothelial cells. Leukemia 2006, 20, 583-589.
93. Janowska-Wieczorek, A.; Marquez, L. A.; Matsuzaki, A.; Hashmi, H. R.; Larratt, L. M.; Boshkov, L. M.; Turner, A. R.; Zhang, M. C.; Edwards, D. R.; Kossakowska, A. E. Expression of matrix metalloproteinases (MMP-2 and-9) and tissue inhibitors of metalloproteinases (TIMP-1 and-2) in acute myelogenous leukaemia blasts: comparison with normal bone marrow cells. Br. J. Haematol. 1999, 105, 402-411.
94. Stefanidakis, M.; Karjalainen, K.; Jaalouk, D. E.; Gahmberg, C. G.; O'Brien, S.; Pasqualini, R.; Arap, W.; Koivunen, E. Role of leukemia cell invadosome in extramedullary infiltration. Blood 2009, 114, 3008-3017.
95. Hatfield, K. J.; Reikvam, H.; Bruserud, O. The crosstalk between the matrix metalloprotease system and the chemokine network in acute myeloid leukemia. Curr. Med. Chem. 2010, 17, 4448-4461.
96. Dias, S.; Hattori, K.; Zhu, Z.; Heissig, B.; Choy, M.; Lane, W.; Wu, Y.; Chadburn, A.; Hyjek, E.; Gill, M., Hicklin, D.J.; Witte, L.; Moore, M. A.; Rafii, S. Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. J. Clin. Invest. 2000, 106, 511-521.
97. Toth, M.; Gervasi, D. C.; Fridman, R. Phorbol ester-induced cell surface association of matrix metalloproteinase-9 in human MCF10A breast epithelial cells. Cancer Res. 1997, 57, 3159-3167.
98. Ambudkar, S. V.; Dey, S.; Hrycyna, C. A.; Ramachandra, M.; Pastan, I.; Gottesman, M. M. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 1999, 39, 361-398.
99. Sonneveld, P.; List, A. F. Chemotherapy resistance in acute myeloid leukaemia. Best Pract. Res. Clin. Haematol. 2001, 14, 211-233.
100. Quiney, C.; Billard, C.; Faussat, A. M.; Salanoubat, C.; Kolb, J. P. Hyperforin inhibits P-gp and BCRP activities in chronic lymphocytic leukaemia cells and myeloid cells. Leuk. Lymphoma 2007, 48, 1587-1599.
101. Doyle, L. A.; Yang, W.; Abruzzo, L. V.; Krogmann, T.; Gao, Y.; Rishi, A. K.; Ross, D. D. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 15665-15670.
102. Ang, C. Y.; Hu, L.; Heinze, T. M.; Cui, Y.; Freeman, J. P.; Kozak, K.; Luo, W.; Liu, F. F.; Mattia, A.; DiNovi, M. Instability of St. John's wort (Hypericum perforatum L.) and degradation of hyperforin in aqueous solutions and functional beverage. J. Agric. Food Chem. 2004, 52, 6156-6164.
103. Martinez-Poveda, B.; Verotta, L.; Bombardelli, E.; Quesada, A. R.; Medina, M. A. Tetrahydrohyperforin and octahydrohyperforin are two new potent inhibitors of angiogenesis. PLoS One 2010, 5, e9558.
104. Cervo, L.; Rozio, M.; Ekalle-Soppo, C. B.; Guiso, G.; Morazzoni, P.; Caccia, S. Role of hyperforin in the antidepressant-like activity of Hypericum perforatum extracts. Psychopharmacology (Berl) 2002, 164, 423-428.
105. Gobbi, M.; Moia, M.; Funicello, M.; Riva, A.; Morazzoni, P.; Mennini, T. In vitro effects of the dicyclohexylammonium salt of hyperforin on interleukin-6 release in different experimental models. Planta Med. 2004, 70, 680-682.
106. Sun, F.; Liu, J. Y.; He, F.; Liu, Z.; Wang, R.; Wang, D. M.; Wang, Y. F.; Yang, D. P. In-vitro antitumor activity evaluation of hyperforin derivatives. J. Asian Nat. Prod. Res. 2011, 13, 688-699.
107. Verotta, L.; Appendino, G.; Belloro, E.; Jakupovic, J.; Bombardelli, E. Furohyperforin, a prenylated phloroglucinol from st. John's wort (Hypericumperforatum). J. Nat. Prod. 1999, 62, 770-772.
108. Verotta, L.; Appendino, G.; Belloro, E.; Bianchi, F.; Sterner, O.; Lovati, M.; Bombardelli, E. Synthesis and biological evaluation of hyperforin analogues. Part I. Modification of the enolized cyclohexanedione moiety. J. Nat. Prod. 2002, 65, 433-438.
109. Chen, X.; Feng, W.; Chen, Q.; Yang, X.; Yang, D.; Wang, D.; Zhong, L. Effects of acetylate hyperforin on the processing of amyloid precursor protein. Int. J. Physiol. Pathophysiol. Pharmacol. 2009, 1, 76-82.
110. Zanoli, P.; Rivasi, M.; Baraldi, C.; Baraldi, M. Pharmacological activity of hyperforin acetate in rats. Behav. Pharmacol. 2002, 13, 645-651.
111. Ploner, C.; Kofler, R.; Villunger, A. Noxa: at the tip of the balance between life and death. Oncogene 2009, 27 (Suppl 1), S84-92.
112. Ghiotto, F.; Fais, F.; Tenca, C.; Tomati, V.; Morabito, F.; Casciaro, S.; Mumot, A.; Zoppoli, G.; Ciccone, E.; Parodi, S.; Bruno, S. Apoptosis of B-cell chronic lymphocytic leukemia cells induced by a novel BH3 peptidomimetic. Cancer Biol. Ther. 2009, 8, 263-271.
113. Billard, C. Design of novel BH3 mimetics for the treatment of chronic lymphocytic leukemia. Leukemia 2012, 26, 2032-2038. doi: 10.1038/leu.2012.88.
114. Maddika, S.; Ande, S. R.; Panigrahi, S.; Paranjothy, T.; Weglarczyk, K.; Zuse, A.; Eshraghi, M.; Manda, K. D.; Wiechec, E.; Los, M. Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist. Updat. 2007, 10, 13-29.
115. Duncan, J. S.; Turowec, J. P.; Vilk, G.; Li, S. S.; Gloor, G. B.; Litchfield, D. W. Regulation of cell proliferation and survival: convergence of protein kinases and caspases. Biochim. Biophys. Acta 2010, 1804, 505-510.
116. Kawamoto, H.; Minato, N. Myeloid cells. Int. J. Biochem. Cell Biol. 2004, 36, 1374-1379.
117. Chen, L. S.; Balakrishnan, K.; Gandhi, V. Inflammation and survival pathways: chronic lymphocytic leukemia as a model system. Biochem. Pharmacol. 2010, 80, 1936-1945.
118. Konopleva, M. Y.; Jordan, C. T. Leukemia stem cells and microenvironment: biology and therapeutic targeting. J. Clin. Oncol. 2010, 29, 591-599.
119. Mohty, M.; Ho, A. D. In and out of the niche: perspectives in mobilization of hematopoietic stem cells. Exp. Hematol. 2011, 39, 723-729.
120. Sison, E. A.; Brown, P. The bone marrow microenvironment and leukemia: biology and therapeutic targeting. Expert Rev. Hematol. 2011, 4, 271-283.
121. Fecteau, J. F. Kipps, T. J. Structure and function of the hematopoietic cancer niche: focus on chronic lymphocytic leukemia. Front Biosci. 2012, 4, 61-73.
122. Kiewert, C.; Buchholzer, M. L.; Hartmann, J.; Chatterjee, S. S.; Klein, J. Stimulation of hippocampal acetylcholine release by hyperforin, a constituent of St. John's Wort. Neurosci. Lett. 2004, 364, 195-198.
123. Gibon, J.; Richaud, P.; Bouron, A. Hyperforin changes the zincstorage capacities of brain cells. Neuropharmacology 2011, 61, 1321-1326.