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Biochemical and chemical characterization of Cynara cardunculus L. extract and its potential use as co-adjuvant therapy of chronic myeloid leukemia

Russo, Antonio, Perri, Mariarita, Cione, Erika, Di Gioia, Maria Luisa, Nardi, Monica, Cristina Caroleo, Maria
Journal of ethnopharmacology 2017 v.202 pp. 184-191
Cynara cardunculus, Mediterranean diet, Western blotting, artichokes, cell proliferation, chromosomes, drug resistance, drug therapy, flowers, gas chromatography-mass spectrometry, human cell lines, humans, leukocytes, messenger RNA, methanol, models, mutation, myeloid leukemia, nuclear magnetic resonance spectroscopy, oncogene proteins, quantitative polymerase chain reaction, reciprocal translocation, recombinant fusion proteins, reverse transcriptase polymerase chain reaction, reversed-phase high performance liquid chromatography, traditional medicine, translation (genetics)
Ancient mediterranean diet was characterized by consuming the spontaneous forms of Cynara cardunculus L. (CCL), commonly called artichoke. Cultivated and/or spontaneous forms of CC studies have demonstrated that methanol extract of CCL flower and/or cynaropicrin showed remarkable anti-proliferative activity in vitro models of leukocyte cancer cell.Chronic myeloid leukemia (CML) is associated with a reciprocal translocation of the long arms of chromosomes 9 and 22 generating the BCR/ABL fusion gene, translated in the p210ᴮCᴿ/ᴬᴮᴸ oncoprotein kinase. This chimeric protein is the target of a kinase inhibitor, imatinib, but the development of mutations in the ABL kinase domain resulting in drug resistance and several approaches to overcoming resistance have been study. In this concern, we investigated the effect of CCL extract on human K562 CML and K562 imatinib resistant (IMAR) cell proliferation and on p210ᴮCᴿ/ᴬᴮᴸ expression.Chemical characterization of the CCL extracts was performed by GC/MS analysis and semipreparative RP-HPLC chromatography. Structural characterization of compounds was assessed by ¹H–¹³C NMR and LC/MS analysis. The effects of CCL extracts on the proliferation of K562 CML human cell line and K562 IMAR were screened by MTT assay. The p210ᴮCᴿ/ᴬᴮᴸ mRNA and protein expressions were analyzed by qRT-PCR and Western blot techniques respectively.We demonstrate that CCL extract affect cell viability of both K562 CML human cell line and K562 IMAR. The biocomponents of CCL were chemical characterized and we identify cynaropicrin and its deacyl derivative having the capability to down-regulate the p210ᴮCᴿ/ᴬᴮᴸ oncoprotein.Our study suggests that the use of those molecules could represent a novel and promising strategy to potentiate the ability of imatinib or of its analogues to induce cancer growth arrest in CML and to delay or overcome the resistance of CML to chemotherapy.