Chemomodulating effects of flavonoids in human leukemia cells

Anti-Cancer Agents in Medicinal Chemistry

Volumn 15, Issue 9, 2015, Pages 1112-1126

  Sak, Katrin ^a   Everaus, Hele ^a  

^a UNIVERSITY OF TARTU   (Estonia)

Author keywords

Chemosensitization; Chemotherapy drugs; Flavonoids; Inhibitory modulation; Leukemia cells; Signaling mechanisms

Indexed keywords

ARSENIC TRIOXIDE; ASPARAGINASE; BLEOMYCIN; BUSULFAN; CISPLATIN; CYTARABINE; DAUNORUBICIN; DECITABINE; DEXAMETHASONE; DOXORUBICIN; ETOPOSIDE; FLAVONOID; FLUDARABINE; IMATINIB; METHOTREXATE; RETINOIC ACID; VINBLASTINE; VINCRISTINE; VORINOSTAT; ANTINEOPLASTIC AGENT;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CELL PROTECTION; CELL VIABILITY; CYTOTOXICITY; DOWN REGULATION; DRUG MECHANISM; HUMAN; LEUKEMIA; NONHUMAN; OXIDATIVE STRESS; UPREGULATION; DRUG POTENTIATION; DRUG SCREENING; PATHOLOGY; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DRUG SCREENING ASSAYS, ANTITUMOR; DRUG SYNERGISM; FLAVONOIDS; HUMANS; LEUKEMIA;

EID: 84952887479     PISSN: 18715206     EISSN: 18755992     Source Type: Journal    
DOI: 10.2174/1871520615666150519112513     Document Type: Article

References (125)

1. Kim, J.H.; Song, M.; Kang, G.H.; Lee, E.R.; Choi, H.Y.; Lee, C.; Kim, J.H.; Kim, Y.; Koo, B.N.; Cho, S.G. Combined treatment of 3-hydroxyflavone and imatinib mesylate increases apoptotic cell death of imatinib mesylate-resistant leukemia cells. Leuk. Res., 2012, 36(9), 1157-1164.
2. Avci, C.B.; Yilmaz, S.; Dogan, Z.O.; Saydam, G.; Dodurga, Y.; Ekiz, H.A.; Kartal, M.; Sahin, F.; Baran, Y.; Gunduz, C. Quercetin- induced apoptosis involves increased hTERT enzyme activity of leukemic cells. Hematology, 2011, 16(5), 303-307.
3. Isoda, H.; Motojima, H.; Onaga, S.; Samet, I.; Villareal, M.O.; Han, J. Analysis of the erythroid differentiation effect of flavonoid apigenin on K562 human chronic leukemia cells. Chem. Biol. Interact., 2014, 220, 269-277.
4. Kikuchi, H.; Yuan, B.; Nishimura, Y.; Imai, M.; Furutani, R.; Kamoi, S.; Seno, M.; Fukushima, S.; Hazama, S.; Hirobe, C.; Ohyama, K.; Hu, X.M.; Takagi, N.; Hirano, T.; Toyoda, H. Cytotoxicity of Vitex agnus-castus fruit extract and its major component, casticin, correlates with differentiation status in leukemia cell lines. Int. J. Oncol., 2013, 43(6), 1976-1984.
5. Chen, H.; Zhang, B.; Yao, Y.; Chen, N.; Chen, X.; Tian, H.; Wang, Z.; Zheng, Q. NADPH oxidase-derived reactive oxygen species are involved in the HL-60 cell monocytic differentiation induced by isoliquiritigenin. Molecules, 2012, 77(11), 13424-13438.
6. Noori-Daloii, M.R.; Saffari, M.; Raoofian, R.; Yekaninejad, M.; Dinehkabodi, O.S.; Noori-Daloii, A.R. The multidrug resistance pumps are inhibited by silibinin and apoptosis induced in K562 and KCL22 leukemia cell lines. Leuk. Res., 2014, 55(5), 575-580.
7. Chang, H.; Lin, H.; Yi, L.; Zhu, J.; Zhou, Y.; Mi, M.; Zhang, Q. 3,6-Dihydroxyflavone induces apoptosis in leukemia HL-60 cell via reactive oxygen species-mediated p38 MAPK/JNK pathway. Eur. J. Pharmacol., 2010, 648(1-3), 31-38.
8. Abubakar, M.B.; Abdullah, W.Z.; Sulaiman, S.A.; Suen, A.B. A review of molecular mechanisms of the anti-leukemic effects of phenolic compounds in honey. Int. J. Mol. Sci., 2012, 15(11), 15054-15073.
9. Huang, A.C.; Cheng, H.Y.; Lin, T.S.; Chen, W.H.; Lin, J.H.; Lin, J.J.; Lu, C.C.; Chiang, J.H.; Hsu, S.C.; Wu, P.P.; Huang, Y.P.; Chung, J.G. Epigallocatechin gallate (EGCG), influences a murine WEHI-3 leukemia model in vivo through enhancing phagocytosis of macrophages and populations of T- and B-cells. In Vivo, 2013, 27(5), 627-634.
10. Chen, Y.J.; Wu, C.S.; Shieh, J.J.; Wu, J.H.; Chen, H.Y.; Chung, T.W.; Chen, Y.K.; Lin, C.C. Baicalein triggers mitochondria- mediated apoptosis and enhances the antileukemic effect of vincristine in childhood acute lymphoblastic leukemia CCRF-CEM cells. Evid. Based Complement. Alternat. Med., 2013; 2013, 124747.
11. Konan, N.A.; Lincopan, N.; Diaz, I.E.; de Fatima Jacysyn, J.; Tiba, M. M.; Amarante Mendes, J.G.; Bacchi, E.M.; Spira, B. Cytotoxicity of cashew flavonoids towards malignant cell lines. Exp. Toxicol. Pathol., 2012, 64(5), 435-440.
12. Youns, M.; Fu, Y.J.; Zu, Y.G.; Kramer, A.; Konkimalla, V.B.; Radlwimmer, B.; Sultmann, H.; Efferth, T. Sensitivity and resistance towards isoliquiritigenin, doxorubicin and methotrexate in T cell acute lymphoblastic leukaemia cell lines by pharmacogenomics. Naunyn. Schmiedebergs. Arch. Pharmacol., 2010, 382(3), 221-234.
13. Benelli, R.; Vene, R.; Ciarlo, M.; Carlone, S.; Barbieri, O.; Ferrari, N. The AKT/NF-kB inhibitor xanthohumol is a potent antilymphocytic leukemia drug overcoming chemoresistance and cell infiltration. Biochem. Pharmacol., 2012, 83(12), 1634-1642.
14. Goto, H.; Yanagimachi, M.; Goto, S.; Takeuchi, M.; Kato, H.; Yokosuka, T.; Kajiwara, R.; Yokota, S. Methylated chrysin reduced cell proliferation, but antagonized cytotoxicity of other anticancer drugs in acute lymphoblastic leukemia. Anticancer Drugs, 2012, 23(4), 417-425.
15. Lee, C.C.; Lin, C.N.; Jow, G.M. Cytotoxic and apoptotic effects of prenylflavonoid artonin B in human acute lymphoblastic leukemia cells. Acta Pharmacol. Sin., 2006, 27(9), 1165-1174.
16. den Boer, M.L.; Pieters, R.; Kazemier, K.M.; Janka-Scaub, G.E.; Henze, G.; Veerman, A.J. The modulating effect of PSC 833, cyclosporin A, verapamil and genistein on in vitro cytotoxicity and intracellular content of daunorubicin in childhood acute lymphoblastic leukemia. Leukemia, 1998, 12(6), 912-920.
17. Cooper, S.L.; Brown, P.A. Treatment of pediatric acute lymphoblactic leukemia. Pediatr. Clin. North Am., 2015, 62(1), 6173.
18. Russo, M.; Spagnuolo, C.; Volpe, S.; Mupo, A.; Tedesco, I.; Russo, G.L. Quercetin induced apoptosis in association with death receptors and fludarabine in cells isolated from chronic lymphocytic leukaemia patients. Br. J. Cancer, 2010, 103(5), 642648.
19. Geeraerts, B.; Vanhoecke, B.; Vanden Berghe, W.; Philippe, J.; Offner, F.; Deforce, D. Deguelin inhibits expression of IkappaBalpha protein and induces apoptosis of B-CLL cells in vitro. Leukemia, 2007, 21(8), 1610-1618.
20. Billard, C.; Menasria, F.; Quiney, C.; Faussat, A.M.; Kolb, J.P. Flavopiridol-induced iNOS downregulation during apoptosis of chronic lymphocytic leukemia cells is caspase-dependent. Leuk. Res., 2008, 32(5), 755-760.
21. Skvarova, K.K.; Fiser, K.; Meistrikova, E.; Rejlova, K.; Zaliova, M.; Fornerod, M.; Drabkin, H.A.; Van den Heuvel-Eibrink, M.M.; Stary, J.; Starkova, J. Homebox gene expression in acute myeloid leukemia is linked to typical underlying molecular aberrations. J. Hematol. Oncol., 2014, 7, 94.
22. Takahashi, S. Epigenetic aberrations in myeloid malignancies. Int. J. Mol. Med., 2013, 32(3), 532-538.
23. Ren, X.; Zhang, Y.; Li, C.; Wang, H.; Jiang, Z.; Zhang, Z.; Guo, Q.; Song, G.; Bi, K.; Jiang, G. Enhancement of baicalin by hexamethylene bisacetamide on the induction of apoptosis contributes to simultaneous activation of the intrinsic and extrinsic apoptotic pathways in human leukemia cells. Oncol. Rep., 2013, 30(5), 2071-2080.
24. Wang, X.; Gocek, E.; Novik, V.; Harrison, J.S.; Danilenko, M.; Studzinski, G.P. Inhibition of Cot1/Tlp2 oncogene in AML cells reduces ERK5 activation and up-regulates p27Kip1 concomitant with enhancement of differentiation and cell cycle arrest induced by silibinin and 1,25-dihydroxyvitamin D(3). Cell Cycle, 2010, 9(22), 4542-4551.
25. Hui, H.; Chen, Y.; Yang, H.; Zhao, K.; Wang, Q.; Zhao, L.; Wang, X.; Li, Z.; Lu, N.; Guo, Q. Oroxylin A has therapeutic potential in acute myelogenous leukemia by dual effects targeting PPARy and RXRa. Int. J. Cancer, 2014, 134(5), 1195-1206.
26. Liesveld, J.L.; Abboud, C.N.; Lu, C.; McNair, C.; Menon, A.; Smith, A.; Rosell, K.; Rapoport, A.P. Flavonoid effects on normal and leukemic cells. Leuk. Res., 2003, 27(6), 517-527.
27. Zhang, J.; Harrison, J.S.; Uskokovic, M.; Danilenko, M.; Studzinski, G.P. Silibinin can induce differentiation as well as enhance vitamin D3-induced differentiation of human AML cells ex vivo and regulates the levels of differentiation-related transcription factors. Hematol. Oncol., 2010, 28(3), 124-132.
28. Kang, S.H.; Jeong, S.J.; Kim, S.H.; Kim, J.H.; Jung, J.H.; Koh, W.; Kim, J.H.; Kim, D.K.; Chen, C.Y.; Kim, S.H. Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling. PLoS One, 2012, 7(4), e28706.
29. Chen, Y.; Hui, H.; Yang, H.; Zhao, K.; Qin, Y.; Gu, C.; Wang, X.; Lu, N.; Guo, Q. Wogonoside induces cell cycle arrest and differentiation by affecting expression and subcellular localization of PLSCR1 in AML cells. Blood, 2013, 121(18), 3682-3691.
30. Britschgi, A.; Simon, H.U.; Tobler, A.; Fey, M.F.; Tschan, M.P. Epigallocatechin-3-gallate induces cell death in acute myeloid leukaemia cells and supports all-trans retinoic acid-induced neutrophil differentiation via death-associated protein kinase 2. Br. J. Haematol., 2010, 149(1), 55-64.
31. Iwasaki, R.; Ito, K.; Ishida, T.; Hamanoue, M.; Adachi, S.; Watanabe, T.; Sato, Y. Catechin, green tea component, causes caspase-independent necrosis-like cell death in chronic myelogenous leukemia. Cancer Sci., 2009, 100(2), 349-356.
32. Jeong, M.H.; Jin, Y.H.; Kang, E.Y.; Jo, W.S.; Park, H.T.; Lee, J.D.; Yoo, Y.J.; Jeong, S.J. The modulation of radiation-induced cell death by genistein in K562 cells: Activation of thymidine kinase 1. Cell Res., 2004, 14(4), 295-302.
33. Lust, S.; Vanhoecke, B.; Van Gele, M.; Philippe, J.; Bracke, M.; Offner, F. The flavonoid tangeretin activates the unfolded protein response and synergizes with imatinib in the erythroleukemia cell line K562. Mol Nutr. Food Res., 2010, 54(6), 823-832.
34. Tolomeo, M.; Grimaudo, S.; Di Cristina, A.; Pipitone, R.M.; Dusonchet, L.; Meli, M.; Crosta, L.; Gebbia, N.; Invidiata, F.P.; Titone, L.; Simoni, D. Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr- Abl expressing leukemia cells. Cancer Lett., 2008, 265(2), 289297.
35. Davenport, A.; Frezza, M.; Shen, M.; Ge, Y.; Huo, C.; Chan, T.H.; Dou, Q.P. Celastrol and an EGCG pro-drug exhibit potent chemosensitizing activity in human leukemia cells. Int. J. Mol. Med., 2010, 25(3), 465-470.
36. Trela, E.; Glowacki, S.; Blasiak, J. Therapy of chronic myeloid leukemia: Twilight of the imatinib era? ISRN Oncol., 2014, 2014: 596483.
37. Lee, C.Y.; Chien, Y.S.; Chiu, T.H.; Huang, W.W.; Lu, C.C.; Chiang, J.H.; Yang, J.S. Apoptosis triggered by vitexin in U937 human leukemia cells via a mitochondrial signaling pathway. Oncol. Rep., 2012, 28(5), 1883-1888.
38. Chen, Y.H.; Chen, H.Y.; Hsu, C.L.; Yen, G.C. Induction of apoptosis by the Lactuca indica L. in human leukemia cell line and its active components. J. Agric. Food Chem., 2007, 55(5), 17431749.
39. Kumar, S.; Pathania, A.S.; Saxena, A.K.; Vishwakarma, R.A.; Ali, A.; Bhushan, S. The anticancer potential of flavonoids isolated from the stem bark of Erythrina suberosa through induction of apoptosis and inhibition of ST AT signaling pathway in human leukemia HL-60 cells. Chem. Biol. Interact., 2013, 205(2), 128137.
40. Wang, L.; Zhang, H.; Chen, B.; Xia, G.; Wang, S.; Cheng, J.; Shao, Z.; Gao, C.; Bao, W.; Tian, L.; Ren, Y.; Xu, P.; Cai, X.; Liu, R.; Wang, X. Effect of magnetic nanoparticles on apoptosis and cell cycle induced by wogonin in Raji cells. Int. J. Nanomed., 2012, 7, 789-798.
41. Baatout, S.; Derradji, H.; Jacquet, P.; Mergeay, M. Increased radiation sensitivity of an eosinophilic cell line following treatment with epigallocatechin-gallate, resveratrol and curcuma. Int. J. Mol. Med., 2005, 75(2), 337-352.
42. Chen, F.Y.; Cao, L.F.; Wan, H.X.; Zhang, M.Y.; Cai, J.Y.; Shen, L.J.; Zhong, J.H.; Zhong, H. Quercetin enhances adriamycin cytotoxicity through induction of apoptosis and regulation of mitogen-activated protein kinase/extracellular signal-regulated kinase/c-Jun N-terminal kinase signaling in multidrug-resistant leukemia K562 cells. Mol Med. Rep., 2015, 11(1), 341-348.
43. Burmistrova, O.; Marrero, M.T.; Estevez, S.; Welsch, I.; Brouard, I.; Quintana, J.; Estevez, F. Synthesis and effects on cell viability of flavonols and 3-methyl ether derivatives on human leukemia cells. Eur. J. Med. Chem., 2014, 84, 30-41.
44. Zhang, X.Y.; Li, W.G.; Wu, Y.J.; Bai, D.C.; Liu, N.F. Proanthocyanidin from grape seeds enhances doxorubicin-induced antitumor effect and reverses drug resistance in doxorubicin- resistant K562/DOX cells. Can. J. Physiol Pharmacol., 2005, 83(3), 309-318.
45. De Martino, L.; D'Arena, G.; Filosa, R.; Peduto, A.; Zeppa, R.; De Feo, V. Natural compounds in anti-leukaemic therapy: A review. Mini Rev. Med. Chem., 2011, 11(6), 492-502.
46. Zhang, X.Y.; Bai, D.C.; Wu, Y.J.; Li, W.G.; Liu, N.F. Proanthocyanidin from grape seeds enhances anti-tumor effect of doxorubicin both in vitro and in vivo. Pharmazie, 2005, 60(1), 533538.
47. Lee, R.; Kim, Y.J.; Lee, Y.J.; Chung, H.W. The selective effect of genistein on the toxicity of bleomycin in normal lymphocytes and HL-60 cells. Toxicology, 2004, 195(2-3), 87-95.
48. Chen, H.; Zhang, B.; Yuan, X.; Yao, Y.; Zhao, H.; Sun, X.; Zheng, Q. Isoliquiritigenin-induced effects on Nrf2 mediated antioxidant defence in the HL-60 cell monocytic differentiation. Cell Biol. Int., 2013, 37(11), 1215-1224.
49. Xu, X.; Zhang, Y.; Li, W.; Miao, H.; Zhang, H.; Zhou, Y.; Li, Z.; You, Q.; Zhao, L.; Guo, Q. Wogonin reverses multi-drug resistance of human myelogenous leukemia K562/A02 cells via donwregulation of MRP1 expression by inhibiting Nrf2/ARE signaling pathway. Biochem. Pharmacol., 2014, 92(2), 220-234.
50. Ohtani, H.; Ikegawa, T.; Honda, Y.; Kohyama, N.; Morimoto, S.; Shoyama, Y.; Juichi, M.; Naito, M.; Tsuruo, T.; Sawada, Y. Effects of various methoxyflavones on vincristine uptake and multidrug resistance to vincristine in P-gp-overexpressing K562/ADM cells. Pharm. Res., 2007, 24(10), 1936-1943.
51. Shen, J.; Zhang, W.; Wu, J.; Zhu, Y. The synergistic reversal effect of multidrug resistance by quercetin and hyperthermia in doxorubicin-resistant human myelogenous leukemia cells. Int. J. Hyperthermia, 2008, 24(2), 151-159.
52. Ji, B.S.; He, L. CJY, an isoflavone, reverses P-glycoprotein- mediated multidrug-resistance in doxorubicin-resistant human myelogenous leukaemia (K562/DOX) cells. J. Pharm. Pharmacol., 2007, 59(7), 1011-1015.
53. Ishii, K.; Tanaka, S.; Kagami, K.; Henmi, K.; Toyoda, H.; Kaise, T.; Hirano, T. Effects of naturally occurring polymethyoxyflavonoids on cell growth, p-glycoprotein function, cell cycle, and apoptosis of daunorubicin-resistant T lymphoblastoid leukemia cells. Cancer Invest., 2010, 28(3), 220-229.
54. Tran, V.H.; Marks, D.; Duke, R.K.; Bebawy, M.; Duke, C.C.; Roufogalis, B.D. Modulation of P-glycoprotein-mediated anticancer drug accumulation, cytotoxicity, and ATPase activity by flavonoid interactions. Nutr. Cancer, 2011, 63(3), 435-443.
55. Palmeira, A.; Sousa, E.; Vasconcelos, M.H.; Pinto, M.M. Three decades of P-gp inhibitors: Skimming through several generations and scaffolds. Curr. Med. Chem., 2012, 19(13), 1946-2025.
56. Ikegawa, T.; Ushigome, F.; Koyabu, N.; Morimoto, S.; Shoyama, Y.; Naito, M.; Tsuruo, T.; Ohtani, H.; Sawada, Y. Inhibition of P- glycoprotein by orange juice components, polymethoxyflavones in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells. Cancer Lett., 2000, 160(1), 21-28.
57. Mates, J.M.; Segura, J.A.; Alonso, F.J.; Marguez, J. Natural antioxidants: Therapeutic prospects for cancer and neurological diseases. Mini Rev. Med. Chem., 2009, 9(10), 1202-1214.
58. Molnar, J.; Engi, H.; Hohmann, J.; Molnar, P.; Deli, J.M.; Wesolowska, O.; Michalak, K.; Wang, Q. Reversal of multidrug resistance by natural substances from plants. Curr. Top. Med. Chem., 2010, 10(17), 1757-1768.
59. Kilani-Jaziri, S.; Frachet, V.; Bhouri, W.; Ghedira, K.; Chekir- Ghedira, L.; Ronot, X. Flavones inhibit the proliferation of human tumor cancer cell lines by inducing apoptosis. Drug Chem. Toxicol, 2012, 35(1), 1-10.
60. Kikuchi, H.; Yuan, B.; Yuhara, E.; Takagi, N.; Toyoda, H. Involvement of histone H3 phosphorylation through p38 MAPK pathway activation in casticin-induced cytocidal effects against the human promyelocytic cell line HL-60. Int. J. Oncol., 2013, 43(6), 2046-2056.
61. Bestwick, C.S.; Milne, L.; Pirie, L.; Duthie, S.J. The effect of short-term kaempferol exposure on reactive oxygen levels and integrity of human (HL-60) leukaemic cells. Biochim. Biophys. Acta, 2005, 1740(3), 340-349.
62. Ruela-de-Sousa, R.R.; Fuhler, G.M.; Blom, N.; Ferreira, C.V.; Aoyama, H.; Peppelenbosch, M.P. Cytotoxicity of apigenin on leukemia cell lines: Implications of prevention and therapy. Cell Death Dis., 2010, 1, e19.
63. Burmistrova, O.; Quintana, J.; Diaz, J.G.; Estevez, F. Astragalin heptaacetate-induced cell death in human leukemia cells is dependent on caspases and activates the MAPK pathway. Cancer Lett., 2011, 309(1), 71-77.
64. Angelo, L.S.; Kurzrock, R. Turmeric and green tea: A recipe for the treatment of B-chronic lymphocytic leukemia. Clin. Cancer Res., 2009, 15(4), 1123-1125.
65. Harikumar, K.B.; Kunnumakkara, A.B.; Ahn, K.S.; Anand, P.; Krishnan, S.; Guha, S.; Aggarwal, B.B. Modification of the cysteine residues in IkappaBalpha kinase and NF-kappaB (p65) by xanthohumol leads to suppression of NF-kappaB-regulated gene products and potentiation of apoptosis in leukemia cells. Blood, 2009, 113(9), 2003-2013.
66. De Vincenzo, R.; Ferlini, C.; Distefano, M.; Gaggini, C.; Riva, A.; Bombardelli, E.; Morazzoni, P.; Valenti, P.; Belluti, F.; Ranelletti, F.O.; Mancuso, S.; Scambia, G. In vitro evaluation of newly developed chalcone analogues in human cancer cells. Cancer Chemother. Pharmacol., 2000, 46(4), 305-312.
67. Kumarappan, C.T.; Mandal, S.C. Antitumor activity of polyphenolic extract of Ichnocarpus frutescens. Exp. Oncol., 2007, 29(2), 94101.
68. Enomoto, R.; Koshiba, C.; Suzuki, C.; Lee, E. Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects. Cancer Chemother. Pharmacol., 2011, 67(5), 1063-1072.
69. Kilani-Jaziri, S.; Neffati, A.; Limem, I.; Boubaker, J.; Skandrani, I.; Sghair, M.B.; Bouhlel, I.; Bhouri, W.; Mariotte, A.M.; Ghedira, K.; Dijoux Franca, M.G.; Chekir-Ghedira, L. Relationship correlation of antioxidant and antiproliferative capacity of Cyperus rotundus pro ducts towards K562 ery thro leukemia cells. Chem. Biol. Interact., 2009, 181(1), 85-94.
70. Ramos, A.M.; Aller, P. Quercetin decreases intracellular GSH content and potentiates the apoptotic action of the antileukemic drug arsenic trioxide in human leukemia cell lines. Biochem. Pharmacol, 2008, 75(10), 1912-1923.
71. Borges-Argaez, R.; Balnbury, L.; Flowers, A.; Gimenez-Turba, A.; Ruiz, G.; Waterman, P.G.; Pena-Rodriguez, L.M. Cytotoxic and antiprotozoal activity of flavonoids from Lonchocarpus spp. Phytomedicine, 2007, 14(7-8), 530-533.
72. Kothan, S.; Dechsupa, S.; Leger, G.; Moretti, J.L.; Vergote, J.; Mankhetkorn, S. Spontaneous mitochondrial membrane potential change during apoptotic induction by quercetin in K562 and K562/adr cells. Can. J. Physiol. Pharmacol., 2004, 82(12), 10841090.
73. Hamblin, T. Natural products and the treatment of leukemia. Leuk. Res., 2006, 30(6), 649-650.
74. Kuete, V.; Ngameni, B.; Wiench, B.; Krusche, B.; Horwedel, C.; Ngadjui, B.T.; Efferth, T. Cytotoxicity and mode of action of four naturally occuring flavonoids from the genus Dorstenia: Gancaonin Q, 4-hydroxylonchocarpin, 6-prenylapigenin, and 6,8- diprenyleriodictyol. Planta Med., 2011, 77(18), 1984-1989.
75. Ravishankar, D.; Rajora, A.K.; Greco, F.; Osborn, H.M. Flavonoids as prospective compounds for anti-cancer therapy. Int. J. Biochem. Cell Biol., 2013, 45(12), 2821-2831.
76. Huang, H.; Liu, N.; Zhao, K.; Zhu, C.; Lu, X.; Li, S.; Lian, W.; Zhou, P.; Dong, X.; Zhao, C.; Guo, H.; Zhang, C.; Yang, C.; Wen, G.; Lu, L.; Li, X.; Guan, L.; Liu, C.; Wang, X.; Dou, Q.P.; Liu, J. Sanggenon C decreases tumor cell viability associated with proteasome inhibition. Front. Biosci. (Elite Ed.), 2011, 3, 13151325.
77. Ghosh, D.; Dey, S.K.; Saha, C. Antagonistic effects of black tea against gamma radiation-induced oxidative damage to normal lymphocytes in comparison with cancerous K562 cells. Radiat. Environ. Biophys., 2014, 53(4), 695-704.
78. Chow, J.M.; Huang, G.C.; Shen, S.C.; Wu, C.Y.; Lin, C.W.; Chen, Y.C. Differential apoptotic effect of wogonin and nor-wogonin via stimulation of ROS production in human leukemia cells. J. Cell. Biochem, 2008, 103(5), 1394-1404.
79. Ko, C.H.; Shen, S.C.; Hsu, C.S.; Chen, Y.C. Mitochondrial- dependent, reactive oxygen species-independent apoptosis by myricetin: roles of protein kinase C, cytochrome c, and caspase cascade. Biochem. Pharmacol., 2005, 69(6), 913-927.
80. Cipak, L.; Rauko, P.; Miadokova, E.; Cipakova, I.; Novotny, L. Effects of flavonoids on cisplatin-induced apoptosis of HL-60 and L1210 leukemia cells. Leuk. Res., 2003, 77(1), 65-72.
81. Ghorbani, A.; Nazari, M.; Jeddi-Tehrani, M.; Zand, H. The citrus flavonoid hesperidin induces p53 and inhibits NF-kB activation in order to trigger apoptosis in NALM-6 cells: involvement of PPARy-dependent mechanism. Eur. J. Nutr., 2012, 51(1), 39-46.
82. Kanno, S.; Tomizawa, A.; Hiura, T.; Osanai, Y.; Shouji, A.; Ujibe, M.; Ohtake, T.; Kimura, K.; Ishikawa, M. Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice. Biol. Pharm. Bull., 2005, 28(3), 527-530.
83. Lee, E.; Enomoto, R.; Koshiba, C.; Hirano, H. Inhibition of P- glycoprotein by wogonin is involved with the potentiation of etoposide-induced apoptosis in cancer cells. Ann. N Y Acad. Sci., 2009, 1171, 132-136.
84. Garg, A.K.; Buchholz, T.A.; Aggarwal, B.B. Chemosensitization and radio sensitization of tumors by plant polyphenols. Antioxid. Redox. Signal., 2005, 7(11-12), 1630-1647.
85. Araujo, K.C.; De M B Costa, E.M.; Pazini, F.; Valadares, M.C.; De Oliveira, V. Bioconversion of quercetin and rutin and the cytotoxicity activities of the transformed products. Food Chem. Toxicol., 2013, 51, 93-96.
86. Brisdelli, F.; Coccia, C.; Cinque, B.; Cifone, M.G.; Bozzi, A. Induction of apoptosis by quercetin: different response of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells. Mol. Cell. Biochem., 2007, 296(1-2), 137-149.
87. Chen, Y.C.; Shen, S.C.; Lin, H.Y. Rutinoside at C7 attenuates the apoptosis-inducing activity of flavonoids. Biochem. Pharmacol., 2003, 66(7), 1139-1150.
88. Bestwick, C.S.; Milne, L. Influence of galangin on HL-60 cell proliferation and survival. Cancer Lett., 2006, 243(1), 80-89.
89. Landis-Piwowar, K.R.; Milacic, V.; Dou, Q.P. Relationship between the methylation status of dietary flavonoids and their growth-inhibitory and apoptosis-inducing activities in human cancer cells. J. Cell. Biochem., 2008, 105(2), 514-523.
90. Mates, J.M.; Segura, J.A.; Alonso, F.J.; Marquez, J. Anticancer antioxidant regulatory functions of phytochemicals. Curr. Med. Chem., 2011, 18(15), 2315-2338.
91. Sak, K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn. Rev., 2014, 8(16), 122-146.
92. Hashemi, M.; Nouri Long, M.; Entezari, M.; Nafisi, S.; Nowroozii H., Anti-mutagenic and pro-apoptotic effects of apigenin on human chronic lymphocytic leukemia cells. Acta Med. Iran., 2010, 48(5), 283-288.
93. Kang, S.N.; Lee, M.H.; Kim, K.M.; Cho, D.; Kim, T.S. Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by silibinin: involvement of protein kinase C. Biochem. Pharmacol, 2001, 61(12), 1487-1495.
94. Bestwick, C.S.; Milne, L.; Duthie, S.J. Kaempferol induced inhibition of HL-60 cell growth results from a heterogeneous response, dominated by cell cycle alterations. Chem. Biol. Interact., 2007, 170(2), 76-85.
95. Chen, W.H.; Chen, Y.; Cui, G.H. Deguelin inhibits expression of IkappaBalpha protein in Raji and U937 cells. Acta Pharmacol. Sin., 2006, 27(4), 485-490.
96. Papazisis, K.T.; Zambouli, D.; Kimoundi, O.T.; Papadakis, E.S.; Vala, V.; Geromichalos, G.D.; Voyatzi, S.; Markala, D.; Destouni, E.; Boutis, L.; Kortsaris, A.H. Protein tyrosine kinase inhibitor, genistein, enhances apoptosis and cell cycle arrest in K562 cells treated with gamma-irradiation. Cancer Lett., 2000, 160(1), 170113.
97. Ciesielska, E.; Wolszczak, M.; Gulanowski, B.; Szulawska, A.; Kochman, A.; Metodiewa, D. In vitro antileukemic, antioxidant and prooxidant activities of Antoksyd S (C/E/XXI): A comparison with baicalin and baicalein. In Vivo, 2004, 18(4), 497-503.
98. Faderl, S.; Estrov, Z. Commentary: Effect of flavonoids on normal and leukemic cells. Leuk. Res., 2003, 27(6), 471-473.
99. Xu, F.; Zhen, Y.S. (-)-Epigallocatechin-3-gallate enhances antitumor effect of cytosine arabinoside on HL-60 cells. Acta Pharmacol. Sin., 2003, 24(2), 163-168.
100. Sanchez, Y.; Calle, C.; De Blas, E.; Aller, P. Modulation of arsenic trioxide-induced apoptosis by genistein and functionally related agents in U937 human leukaemia cells. Regulation by ROS and mitogen-activated protein kinases. Chem. Biol. Interact., 2009, 182(1), 37-44.
101. Freund, A.; Boos, J.; Harkin, S.; Schultze-Mosgau, M.; Veerman, G.; Peters, G.J.; Gescher, A. Augmentation of 1-beta-D- arabinofuranosylcytosine (Ara-C) cytotoxicity in leukaemia cells by co-administration with anti signalling drugs. Eur. J. Cancer, 1998, 34(6), 895-901.
102. Teofili, L.; Pierelli, L.; Iovino, M.S.; Leone, G.; Scambia, G.; De Vincenzo, R.; Benedetti-Panici, P.; Menichella, G.; Macri, E.; Piantelli, M.; Ranelletti, F.O.; Larocca, L.M. The combination of quercetin and cytosine arabinoside synergistically inhibits leukemic cell growth. Leuk. Res., 1992, 16(5), 497-503.
103. Raynal, N.J.; Charbonneau, M.; Momparler, L.F.; Momparler, R.L. Synergistic effect of 5-Aza-2'-deoxycytidine and genistein in combination against leukemia. Oncol. Res., 2008, 17(5), 223-230.
104. Huang, Y.; Hu, J.; Zheng, J.; Li, J.; Wei, T.; Zheng, Z.; Chen, Y. Down-regulation of the PI3K/Akt signaling pathway and induction of apoptosis in CA46 Burkitt lymphoma cells by baicalin. J. Exp. Clin. Cancer Res., 2012, 31, 48.
105. Bortul, R.; Tazzari, P.L.; Billi, A.M.; Tabellini, G.; Mantovani, I.; Cappellini, A.; Grafone, T.; Martinelli, G.; Conte, R.; Martelli, A.M. Deguelin, a PI3K/AKT inhibitor, enhances chemosensitivity of leukaemia cells with an active PI3K/AKT pathway. Br. J. Haematol., 2005, 129(5), 677-686.
106. Wang, Y.; Miao, H.; Li, W.; Yao, J.; Sun, Y.; Li. Z.; Zhao, L.; Guo, Q. CXCL12/CXCR4 axis confers adriamycin resistance to human chronic myelogenous leukemia and oroxylin A improves the sensitivity of K562/ADM cells. Biochem. Pharmacol., 2014, 90(3), 212-225.
107. Otsuyama, K.I.; Ma, Z.; Abroun, S.; Amin, J.; Shamsasenjan, K.; Asaoku, H.; Kawano, M.M. PPARbeta-mediated growth suppression of baicalein and dexamethasone in human myeloma cells. Leukemia, 2007, 21(1), 187-190.
108. Sanchez, Y.; Amran, D.; Fernandez, C.; de Blas, E.; Aller, P. Genistein selectively potentiates arsenic trioxide-induced apoptosis in human leukemia cells via reactive oxygen species generation and activation of reactive oxygen species-inducible protein kinases (p38-MAPK, AMPK). Int. J. Cancer, 2008, 123(5), 1205-1214.
109. De Souza Reis, F.R.; De Faria, F.C.; Castro, C.P.; De Souza, P.S.; Da Cunha Vasconcelos, F.; Bello, R.D.; Da Silva, A.J.; Costa, P.R.; Maia, R.C. The therapeutical potential of a novel pterocarpanquinone LQB-118 to target inhibitor of apoptosis proteins in acute myeloid leukemia cells. Anticancer Agents Med. Chem., 2013, 13(2), 341351.
110. Abdallah, H.M.; Al-Abd, A.M.; El-Dine, R.S.; El-Halawany, A.M. P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review. J. Adv. Res., 2015, 6(1), 45-62.
111. 4 and wogonin on the reversal of multidrug resistance in K562/A02 cell line. Int. J. Nanomedicine, 2012, 7, 2843-2852.
112. Lee, E.; Enomoto, R.; Suzuki, C.; Ohno, M.; Ohashi, T.; Miyauchi, A.; Tanimoto, E.; Maeda, K.; Hirano, H.; Yokoi, T.; Sugahara, C. Wogonin, a plant flavone, potentiates etoposide-induced apoptosis in cancer cells. Ann. N YAcad. Sci., 2007, 1095, 521-526.
113. Elbling, L.; Weiss, R.M.; Teufelhofer, O.; Uhl, M.; Knasmueller, S.; Schulte-Hermann, R.; Berger, W.; Micksche, M. Green tea extract and (-)-epigallocatechin-3-gallate, the major tea catechin, exert oxidant but lack antioxidant activities. FASEB J., 2005, 19(7), 807-809.
114. Baran, I.; Ionescu, D.; Filippi, A.; Mocanu, M.M.; Iftime, A.; Babes, R.; Tofolean, I.T.; Irimia, R.; Goicea, A.; Popescu, V.; Dimancea, A.; Neagu, A.; Ganea, C. Novel insights into the antiproliferative effects and synergism of quercetin and menadione in human leukemia Jurkat T cells. Leuk. Res., 2014, 38(7), 836849.
115. Baran, I.; Ganea, C.; Scordino, A.; Musumeci, F.; Barresi, V.; Tudisco, S.; Privitera, S.; Grasso, R.; Condorelli, D.F.; Ursu, I.; Baran, V.; Katona, E.; Mocanu, M.M.; Gulino, M.; Ungureanu, R.; Surcel, M.; Ursaciuc, C. Effects of menadione, hydrogen peroxide, and quercetin on apoptosis and delayed luminescence of human leukemia Jurkat T-cells. Cell Biochem. Biophys., 2010, 58(3), 169179.
116. Baran, I.; Ganea, C.; Privitera, S.; Scordino, A.; Barresi, V.; Musumeci, F.; Mocanu, M.M.; Condorelli, D.F.; Ursu, I.; Grasso, R.; Gulino, M.; Garaiman, A.; Musso, N.; Cirrone, G.A.; Cuttone, G. Detailed analysis of apoptosis and delayed luminescence of human leukemia Jurkat T cells after proton irradiation and treatments with oxidant agents and flavonoids. Oxid. Med. Cell. Longev, 2012,2012, 498914.
117. Lanoue, L.; Green, K.K.; Kwik-Uribe, C.; Keen, C.L. Dietary factors and the risk for acute infant leukemia: evaluating the effects of cocoa-derived flavanols on DNA topoisomerase activity. Exp. Biol. Med. (Maywood), 2010, 235(1), 77-89.
118. Khonkarn, R.; Mankhetkorn, S.; Hennink, W.E.; Okonogi, S. PEG- OCL micelles for quercetin solubilization and inhibition of cancer cell growth. Eur. J. Pharm. Biopharm., 2011, 79(2), 268-275.
119. Singh, M.; Bhatnagar, P.; Srivastava, A.K.; Kumar, P.; Shukla, Y.; Gupta, K.C. Enhancement of cancer chemosensitization potential of cisplatin by tea polyphenols poly(lactide-co-glycolide) nanoparticles. J. Biomed. Nanotechnol., 2011, 7(1), 202.
120. Baumann, S.; Fas, S.C.; Giaisi, M.; Muller, W.W.; Merling, A.; Gulow, K.; Edler, L.; Krammer, P.H., Li-Weber, M. Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLCgamma1- and Ca2+-dependent apoptosis. Blood, 2008, 111(4), 2354-2363.
121. Boubaker, J.; Ben Sghaier, M.; Skandrani, I.; Ghedira, K., Chekir-Ghedira, L. Isorhamnetin 3-O-robinobioside from Nitraria retusa leaves enhance antioxidant and antigenotoxic activity in human chronic myelogenous leukemia cell line K562. BMC Complement. Altern. Med., 2012, 12, 135.
122. Larocca, L.M.; Ranelletti, F.O.; Maggiano, N.; Rutella, S.; La Barbera E.O.; Rumi, C.; Serra, F.; Voso, M.T.; Piantelli, M.; Teofili, L.; Leone, G. Differential sensitivity of leukemic and normal hematopoietic progenitors to the killing effect of hyperthermia and quercetin used in combination: role of heat-shock protein-70. Int. J. Cancer, 1997, 73(1), 75-83.
123. Almenara, J.; Rosato, R.; Grant, S. Synergistic induction of mitochondrial damage and apoptosis in human leukemia cells by flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Leukemia, 2002, 16(1), 1331-1343.
124. Herst, P.M.; Petersen, T.; Jerram, P.; Baty, J.; Berridge, M.V. The antiproliferative effects of phenoxodiol are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells. Biochem. Pharmacol., 2007, 74(11), 1587-1595.
125. Hoffman, R.; Graham, L.; Newlands, E.S. Enhanced antiproliferative action of busulphan by quercetin on the human leukaemia cell line K562. Br. J. Cancer, 1989, 59(3), 347-348.