title: The multidrug resistance pumps are inhibited by silibinin and apoptosis induced in K562 and KCL22 leukemia cell lines.
abstract: Silibinin have been introduced for several years as a potent antioxidant in the field of nutraceuticals. Based on wide persuasive effects of this drug, we have decided to investigate the effects of silibinin on chronic myelogenous leukemia (CML) in vitro models, K562 and KCL22 cell lines. Lactate dehydrogenase (LDH) release, microculture tetrazolium test (MTT assay) and real-time PCR were employed to evaluate the effects of silibinin on cell cytotoxicity, cell proliferation and expression of various multidrug resistance genes in these cell lines, respectively. Our results have shown that presence of silibinin has inhibitory effects on cell proliferation of K562 and KCL22 cell lines. Also, our data indicated that silibinin, in a dose-dependent manner with applying no cytotoxic effects, inhibited cell proliferation and reduced mRNA expression levels of some transporter genes e.g. MDR1, MRP3, MRP2, MRP1, MRP5, MRP4, ABCG2, ABCB11, MRP6 and MRP7. The multifarious in vitro inhibitory effects of silibinin are in agreement with growing body of evidence that silibinin would be an efficient anticancer agent in order to be used in multi-target therapy to prevail the therapeutic hold backs against CML.
authors: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: nooridaloii@sina.tums.ac.ir.
authors: Mohammad Reza
authors: MR
authors: Noori-Daloii
authors: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mojtaba
authors: M
authors: Saffari
authors: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Reza
authors: R
authors: Raoofian
authors: Department of Biostatistics, School of Public Health and Institute of Public Health Research, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mirsaeed
authors: M
authors: Yekaninejad
authors: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Orkideh Saydi
authors: OS
authors: Dinehkabodi
authors: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Ali Reza
authors: AR
authors: Noori-Daloii
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000077385:Silybin; D012838:Silymarin
keywords: Chronic myelogenous leukemia; K562 cell line; KCL22 cell line; Silibinin; Transporter genes