Apoptotic events induced by synthetic naphthylchalcones in human acute leukemia cell lines

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• 作者：Mariana Franzoni Maioral^a ; ^{marimaioral@gmail.com} ; Pâ ; mela Cristina Gaspar^a ; Gabriela Regina Rosa Souza^a ; Alessandra Mascarello^b ; Louise Domeneghini Chiaradia^b ; Marley Aparecida Lic&iacute ; nio^a ; Ana Carolina Rabello Moraes^a ; Rosendo Augusto Yunes^b ; Ricardo José ; Nunes^b ; Maria Clá ; udia Santos-Silva^a
• 关键词：Leukemia ; Chalcones ; Cytotoxicity ; Apoptosis ; Cell cycle
• 刊名：Biochimie
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：95
• 期：4
• 页码：866-874
• 全文大小：937 K

文摘

Acute leukemia is a disorder of the hematopoietic system characterized by the expansion of a clonal population of cells blocked from differentiating into mature cells. Recent studies have shown that chalcones and their derivatives induce apoptosis in different cell lines. Since new compounds with biological activity are needed, the aim of this study was to evaluate the cytotoxic effect of three synthetic chalcones, derived from 1-naphthaldehyde and 2-naphthaldehyde, on human acute myeloid leukemia K562 cells and on human acute lymphoblastic leukemia Jurkat cells. Based on the results, the most cytotoxic compound (A1) was chosen for further analysis in six human acute leukemia cells and in a human colon adenocarcinoma cell line (HT-29). Chalcone A1 significantly reduced the cell viability of K562, Jurkat, Kasumi, U937, CEM and NB4 cells in a concentration and time-dependent manner when compared with the control group (IC₅₀ values between ¡«1.5?¦ÌM and 40?¦ÌM). It was also cytotoxic to HL-29 cells. To further examine its effect on normal cells, peripheral blood lymphocytes collected from healthy volunteers were incubated with the compound. It has also been incubated with human fibroblasts cultured from bone marrow (JMA). Chalcone A1 is non-cytotoxic to PBL cells and to JMA cells. A1 caused significant cell cycle arrest in all phases according to the cell line, and increased the proportion of cells in the sub G0/G1 phase. To evaluate whether this chalcone induced cell death via an apoptotic or necrotic pathway, cell morphology was examined using fluorescence microscopy. Cells treated with A1 at IC₅₀ demonstrated the morphological characteristic of apoptosis, such as chromatin condensation and formation of apoptotic bodies. Apoptosis was confirmed by externalization of phosphatidylserine, which was detected by the Annexin V-FITC method, and by DNA fragmentation. The results suggest that chalcone A1 has potential as a new lead compound for cancer therapy.