wogonin and Leukemia--Erythroblastic--Acute

Wogonin (5,7-dihydroxy-8-methoxyflavone) is one of the active components of flavonoids isolated from Scutellariae radix and possesses antitumor effect against leukemia. Cadmium-telluride quantum dots (CdTe-QDs) are a kind of nanoparticles with great potential in functioning as an efficient drug delivery vector in biomedical research. In this study, we investigated the synergistic effect of CdTe-QDs with Wogonin on the induction of apoptosis using drug-resistant human leukemia KA cells. Flow cytometry analysis, assay of morphology under electron microscope, quantitative analysis of tumor volume and micro-CT imaging demonstrated that compared with that by pure CdTe-QDs or wogonin, the apoptosis rate increased sharply when treated wirh CdTe-QDs together with wogonin on KA cells. These results proved that the nanocomposites readily overcame the barrier of drug-resistance and provoked cell apoptosis in vitro and in vivo by facilitating the interaction between wogonin and KA cells. As known to all, it is an inevitable tendency that new effective therapies will take the place of conventional chemotherapy and radiotherapy presenting significant disadvantages. According to this article, CdTe-QD combined with wogonin is a possible alternative for some cancer treatments.

Topics: Animals; Apoptosis; Cadmium Compounds; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Flavanones; Heterografts; Humans; K562 Cells; Leukemia, Erythroblastic, Acute; Mice; Mice, Nude; Microscopy, Electron, Transmission; Quantum Dots; Tellurium; X-Ray Microtomography

Wogonin, a flavonoid derived from Scutellaria baicalensis Georgi, has been demonstrated to be highly effective in treating hematologic malignancies. In this study, we investigated the anticancer effects of wogonin on K562 cells, K562 imatinib-resistant cells, and primary patient-derived CML cells. Wogonin up-regulated transcription factor GATA-1 and enhanced binding between GATA-1 and FOG-1, thereby increasing expression of erythroid-differentiation genes. Wogonin also up-regulated the expression of p21 and induced cell cycle arrest. Studies employing benzidine staining and analyses of cell surface markers glycophorin A (GPA) and CD71 indicated that wogonin promoted differentiation of K562, imatinib-resistant K562, and primary patient-derived CML cells. Wogonin also enhanced binding between GATA-1 and MEK, resulting in inhibition of the growth of CML cells. Additionally, in vivo studies showed that wogonin decreased the number of CML cells and prolonged survival of NOD/SCID mice injected with K562 and imatinib-resistant K562 cells. These data suggested that wogonin induces cycle arrest and erythroid differentiation in vitro and inhibits proliferation in vivo.

Topics: Animals; Antineoplastic Agents; Benzamides; Cell Cycle Checkpoints; Cell Differentiation; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Erythroid Cells; Extracellular Signal-Regulated MAP Kinases; Female; Flavanones; GATA1 Transcription Factor; Humans; Imatinib Mesylate; K562 Cells; Leukemia, Erythroblastic, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; MAP Kinase Kinase Kinases; Mice, Inbred NOD; Mice, SCID; Nuclear Proteins; Piperazines; Protein Kinase Inhibitors; Pyrimidines; RNA Interference; Signal Transduction; Time Factors; Transcription Factors; Transfection; Tumor Cells, Cultured; Xenograft Model Antitumor Assays