Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

Background: Flavonoids are natural compounds with antioxidant, anticarcinogenic, and anti-inflammatory effects.Aims: To determine the cytotoxic effects of flavonoids and drug resistance related to P-gp on K562 human chronic myeloid leukemia cells. We also aimed to evaluate the therapeutic potential of imatinib and flavonoid combinations.Study Design: Cell culture study.Methods: In this study, K562 cells were treated with apigenin, luteolin, 5-desmethyl sinensetin and the anticancer drug imatinib mesylate. The effect of flavonoids on K562 cell proliferation was detected using the 3-(4,5-dimethylthiazolyl)2,5‑diphenyl‑tetrazolium bromide assay. Concentrations of apigenin, luteolin, and 5-desmethyl sinensetin ranging from 25 to 200 μM and of imatinib from 5 to 50 μM administered for 72 h were studied. Apoptosis/necrosis and P-gp activity were measured using flow cytometry. The combined effects of different concentrations of flavonoids with imatinib were evaluated according to combination index values calculated using CompuSyn software.Results: In our study, the IC50 values for apigenin, luteolin, and 5-desmethyl sinensetin were found to be 140 μM, 100 μM, and >200 μM, respectively. Luteolin (100 μM) had the highest cytotoxic activity of these flavonoids. These results were statistically significant (p

___

  • Calderón-Montano JM, Burgos-Morón E, Pérez-Guerrero C, López-Lázaro M. A Review on the Dietary Flavonoid Kaempferol. Mini Rev Med Chem 2011;11:298-344.
  • Knekt P, Kumpulainen J, Jarvinen R, Rissanen H, Heliovaara M, Reunanen A, et al. Flavonoid intake and risk of chronic diseases. Am J Clin Nutr 2002;76:560-8.
  • Bors W, Heller W, Michel C, Saran M. Flavonoid as antioxidants: Determination of radical-scavenging efficiencies. Methods Enzimol 1990;186:343-55.
  • Menezes JC, Orlikova B, Morceau F, Diederich M. Natural And Synthetic Flavonoids. Structure Activity Relationship And Chemotherapeutic Potential For The Treatment of Leukemia. Crit Rev Food Sci Nutr 2016;(Suppl 56):4-28.
  • Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Scientific World Journal 2013;2013:162750.
  • Birman H. Bioactivities of plant flavonoids and the possible action mechanisms. J Ist Faculty Med 2012;75:46-9.
  • Koçyildiz ZC, Birman H, Olgaç V, Akgün-Dar K, Melikoğlu G, Meriçli AH. Crataegus tanacetifolia leaf extract prevents L-NAME-induced hypertension in rats: A morphological study. Phytother Res 2006;20:66-70.
  • Kozłowska A, Szostak-Wegierek D. Flavonoids food sources and health benefits. Rocz Panstw Zakl Hig 2014;65:79-85.
  • Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev 2014;8:122-46.
  • Wei G, Rafiyath S, Liu D. First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib. J Hematol Oncol 2010;3:47.
  • Solmaz S, Adan Gokbulut A, Cincin B, Ozdogu H, Boga C, Cakmakoglu B, et al. Therapeutic potential of apigenin, a plant flavonoid, for imatinib-sensitive and resistant chronic myeloid leukemia cells. Nutr Cancer 2014;66:599-612.
  • Ramalhete C, Molnar J, Mulhovo S, Rosario VE, Ferreira MJ. New potent P-glycoprotein modulators with the cucurbitane scaffold and their synergistic interaction with doxorubicin on resistant cancer cells. Bioorg Med Chem 2009;17:6942-51.
  • Li Y, Wang H, Zhang R, Zhang G, Yang Y, Liu Z. Biofabrication of polyphenols coated Nano palladium and its in-vitro cytotoxicity against human leukemia cell lines (K562). J Photochem Photobiol B 2017;175:173-7.
  • Sak K, Everaus H. Established Human Cell Lines as Models to Study Anti-leukemic Effects of Flavonoids. Curr Genomics 2017;18:3-26.
  • Tran TP, Kim HG, Choi JH, Na MK, Jeong HG. Reversal of P-glycoprotein-mediated multidrug resistance is induced by mollugin in MCF-7/adriamycin cells. Phytomedicine 2012;20:622-31.
  • Covelli A. Modulation of multidrug resistance (MDR) in hematological malignancies. Ann Oncol 1999;10(Suppl 6):53-9.
  • Mahon FX, Belloc F, Lagarde V, Chollet C, Moreau-Gaudry F, Reiffers J, et al. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 2003;101:2368-73.
  • Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006;58:621-81.
  • Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.
  • Zhang N, Fu JN, Chou TC. Synergistic combination of microtubule targeting anticancer fludelone with cytoprotective panaxytriol derived from panax ginseng against MX-1 cells in vitro: experimental design and data analysis using the combination index method. Am J Cancer Res 2016;6:97-104.
  • Chou TC. Drug combination Studies and their synergy quantification using the Chou-Talalay method. Cancer Res 2010;70:440-6.
  • Sak K, Everaus H. Chemomodulating Effects of Flavonoids in Human Leukemia Cells. Anticancer Agents Med Chem 2015;15:1112-26.
  • Qiao H, Wang TY, Yan W, Qin A, Fan QM, Han XG, et al. Synergistic suppression of human breast cancer cells by combination of plumbagin and zoledronic acid in vitro. Acta Pharmacol Sin 2015;36:1085-98.
  • Sghaiera MB, Skandrani I, Nasra N, Francac MG, Chekir-Ghediraa L, Ghediraa K. Flavonoids and sesquiterpenes from Tecurium ramosissimum promote antiproliferation of human cancer cells and enhance: antioxidant activity: A structure-activity relationship study. Environ Toxicol Pharmacol 2011;32:336-48.
  • Rossi M, Lugo A, Lagiou P, Zucchetto A, Polesel J, Serraino D, et al. Proanthocyanidins and other flavonoids in relation to pancreatic cancer: a case-control study in Italy. Ann Oncol 2012;23:1488-93.
  • Choi EJ. Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: involvement of CDK4 and p21. Nutr Cancer 2007;59:115-9.
  • Leopoldini M, Pitarch IP, Russo N, Toscano M. Structure. Conformation, and electronic properties of apigenin, luteolin, and taxifolin antioxidants. A first principle theoretical study. J Phys Chem A 2004;108:92-6.
  • Bernardo PS, Reis FR, Maia RC. Imatinib increases apoptosis index through modulation of survivin subcellular localization in the blast phase of CML cells. Leuk Res 2012;36:1510-6.
  • Drullion C, Trégoat C, Lagarde V, Tan S, Gioia R, Priault M, et al. Apoptosis and autophagy have opposite roles on imatinib-induced K562 leukemia cell senescence. Cell Death Dis 2012;3:373.
  • Lompardía SL, Díaz M, Papademetrio DL, Pibuel M, Álvarez É, Hajos SE. 4-methylumbelliferone and imatinib combination enhances senescence induction in chronic myeloid leukemia cell lines. Invest New Drugs 2016;35:1-10.
  • Gómez-Casares MT, García-Alegria E, López-Jorge CE, Ferrándiz N, Blanco R, Alvarez S, et al. MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through downregulation of p27 (KIP1.) Oncogene 2013;32:2239-46.
  • Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B, et al. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif 2012;45:487-98.
  • Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia: Elsevier; 2015.
  • Ramirez P, DiPersio JF. Therapy options in imatinib failures. Oncologist 2008;13:424-34.
  • Illmer T, Schaich M, Platzbecker U, Freiberg-Richter J, Oelschlagel U, von Bonin M, et al. P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate. Leukemia 2004;18:401-9.
  • Nestal de Moraes G, Souza PS, Costas FC, Vasconcelos FC, Reis FR, Maia RC. The interface between BCR-ABL-dependent and -independent resistance signaling pathways in chronic myeloid leukemia. Leukemia Res Treatment 2012;2012:671702.
  • Chen FY, Cao LF, Wan HX, Zhang MY, Cai JY, Shen LJ, et al. Quercetin enhance 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;11:341-8.
  • Khajapeer KV, Baskaran R. Natural Products for Treatment of Chronic Myeloid Leukemia. InTech 2016.
  • Souza PS, Vasconcelos FC, De Souza Reis FR, Nestal De Moraes G, Maia RC. P-glycoprotein and survivin simultaneously regulate vincristine-induced apoptosis in chronic myeloid leukemia cells. Int J Oncol 2011;39:925-33.
  • Kong W, Hooper KM, Ganea D. The natural dual cyclooxygenase and 5-lipoxygenase inhibitor flavocoxid is protective in EAE through effects on Th1/Th17 differentiation and macrophage/microglia activation. Brain Behav Immun 2016;53:59-71.
Balkan Medical Journal-Cover
  • ISSN: 2146-3123
  • Başlangıç: 2015
  • Yayıncı: Erkan Mor
Sayıdaki Diğer Makaleler

Neutrophil Gelatinase-associated Lipocalin Significantly Correlates with Ischemic Damage in Patients Undergoing Laparoscopic Partial Nephrectomy

Isbara Alp ENİŞTE, Meltem SAVRAN KARADENİZ, Tzevat TEFİK, Sebahat USTA, Kamil PEMBECİ, Hayriye Şentürk ÇİFTCİ, Öner ŞANLI, Kamil Mehmet TUĞRUL

Detection of Ascaris lumbricoides by Capsule Endoscopy

Azamat Kh. KADE, Andrey V. AVAKIMYAN, Pavel P. POLIAKOV, Anar Y. ALIMETOV, Alexandr V. ONOPRIEV

Balkan Medical Journal and Legal Regulation

Zafer KOÇAK, Cem UZUN, Mustafa İNAN, Hakan ERBAŞ

Validation of the “Mind the Gap” Scale to Assess Satisfaction with Health Care among Adolescents

Berna EREN FİDANCI, Dilek YILDIZ, Evrim KIZILER

The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies

Fulya Öz PUYAN, Serhan ALKAN

A Short History of Trakya University Faculty of Medicine

Recep MESUT

Effectiveness of Percutaneous Intradiscal Decompression Therapy in Thoracic Disc Herniation

İbrahim AŞIK, Güngör Enver ÖZGENCİL, Burak ERKEN, Ayşegül CEYLAN

Evaluation of Cerebral Blood Flow Alterations and Acute Neuronal Damage due to Water-Pipe Smoking

Uygar UTKU, Serkan YILMAZ, Onur KARAKAYALI

Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

Hüsniye BİRMAN, Gülay MELİKOĞLU, Serap KURUCA, Ferdane DANIŞMAN KALINDEMİRTAŞ, Eda CANDÖKEN, Sema Bilgiç GAZİOĞLU

No Family Clustering in Behçet’s Syndrome

Mehmet Engin TEZCAN