1. Biochemical and chemical characterization of Cynara cardunculus L. extract and its potential use as co-adjuvant therapy of chronic myeloid leukemia
- Author
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Maria Cristina Caroleo, Antonio Russo, Erika Cione, Monica Nardi, Mariarita Perri, Maria Luisa Di Gioia, Russo, A., Perri, M., Cione, E., Di Gioia, M., Nardi, M., and Cristina Caroleo, M.
- Subjects
Cynara cardunculus L ,Sesquiterpene ,0301 basic medicine ,Settore MED/06 - Oncologia Medica ,Fusion Proteins, bcr-abl ,Pharmacology ,Antineoplastic Agent ,Lactones ,chemistry.chemical_compound ,0302 clinical medicine ,hemic and lymphatic diseases ,Drug Discovery ,K562 cell ,ABL ,Chemistry ,Chronic myeloid leukemia ,breakpoint cluster region ,Myeloid leukemia ,Lactone ,Cynaropicrin ,Imatinib resistant ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,K562 cells ,P210BCR/ABLoncoprotein ,Antineoplastic Agents ,Antineoplastic Agents, Phytogenic ,Cell Survival ,Cynara ,Drug Resistance, Neoplasm ,Humans ,K562 Cells ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Plant Extracts ,Sesquiterpenes ,Drug Discovery3003 Pharmaceutical Science ,Human ,medicine.drug ,Plant Extract ,03 medical and health sciences ,medicine ,Viability assay ,neoplasms ,Cell growth ,Imatinib ,030104 developmental biology ,Cancer research - Abstract
Ethnopharmacological relevance 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. Aim of the study 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 p210 BCR/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 p210 BCR/ABL expression. Materials and methods Chemical characterization of the CCL extracts was performed by GC/MS analysis and semipreparative RP-HPLC chromatography. Structural characterization of compounds was assessed by 1 H– 13 C 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 p210 BCR/ABL mRNA and protein expressions were analyzed by qRT-PCR and Western blot techniques respectively. Results 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 p210 BCR/ABL oncoprotein. Conclusions 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.
- Published
- 2017