title: Therapeutic potential of apigenin, a plant flavonoid, for imatinib-sensitive and resistant chronic myeloid leukemia cells.
abstract: Despite the presence of many therapeutic regimens like imatinib and other tyrosine kinase inhibitors, the development of resistance, intolerance, and side effects makes chronic myeloid leukemia (CML) therapy challenging. Thus, there is a need to discover novel drugs for CML patients. In this study, we attempted to assess apigenin, a common plant dietary flavonoid, in terms of its cytotoxic, apoptotic, and cytostatic effects on imatinib-sensitive and resistant Philadelphia-positive CML cells. We analyzed apigenin's effects on cell proliferation, apoptosis, caspase-3 activity, loss of mitochondrial membrane potential, and cell cycle progression in K562 and K562/IMA3 cells. Furthermore, we described genes and gene networks that are modulated in CML in response to apigenin. Results of our study revealed that apigenin has cytotoxic and apoptotic effects on both cell types. We also displayed that apigenin induced G2/M arrest in K562 cells while arresting K562/IMA3 cells in S phase especially at the highest apigenin concentration. The expression analysis identified a set of genes that were regulated by apigenin in K652 and K562/IMA3 cells. Association of modulated genes with biological functional groups identified several networks affected by apigenin including cell survival, proliferation, cell death, cell cycle, and cell signalling pathways.
authors.affiliation: a Department of Hematology, Adana Teaching and Medical Research Center , Baskent University , Adana , Turkey.
authors.forename: Soner
authors.initials: S
authors.lastname: Solmaz
authors.forename: Aysun
authors.initials: A
authors.lastname: Adan Gokbulut
authors.forename: Birsu
authors.initials: B
authors.lastname: Cincin
authors.forename: Hakan
authors.initials: H
authors.lastname: Ozdogu
authors.forename: Can
authors.initials: C
authors.lastname: Boga
authors.forename: Bedia
authors.initials: B
authors.lastname: Cakmakoglu
authors.forename: Ilknur
authors.initials: I
authors.lastname: Kozanoglu
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Baran
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D047310:Apigenin; D000068877:Imatinib Mesylate; C505407:CASP3 protein, human; D053148:Caspase 3