Induction of apoptosis and differentiation by atractylenolide-1 isolated from Atractylodes macrocephala in human leukemia cells

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• 作者：Huey-Lan Huang<sup>asup> ; Tzu-Wen Lin<sup>bsup> ; Yu-Ling Huang<sup>csup> ; Ray-Ling Huang<sup>bsup><sup> ; sup><sup>x00002093@meiho.edu.tw" class="auth_mail" title="E-mail the corresponding authorsup>
• 关键词：AML ; acute myeloblastic leukemia ; A. macrocephula ; Atractylodes macrocephula ; ATL-I ; atractylenolide I ; CML ; chronic myeloblastic leukemia ; DMEM ; Dulbecco&rsquo ; s modified Eagle&rsquo ; s medium ; DMSO ; dimethyl sulfoxide ; ELISA ; enzyme-linked immunosorbent assay ; HRP ; horseradish peroxidase ; IC50 ; 50% growth inhibition concentration value ; MFI ; mean fluorescent intensity ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyl tetrazolium bromide ; OD ; optical density ; SDS&ndash ; PAGE ; sodium dodecylsulfate&
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：26
• 期：8
• 页码：1905-1909
• 全文大小：744 K

文摘

Atractylodes macrocephula Koidz (A. macrocephula, also known as Baizhu) is an important ingredient in several traditional Chinese herb complexes for the treatment of abdominal pain and gastroenterology diseases for thousands of years. We previously demonstrated the induction of ROS-mediated apoptosis by methanol extract of A. macrocephula in human leukemia cells. After purification and assessment of those active compounds from A. macrocephula ethanol extracts, in this study, we focused on the major active compound, atractylenolide I (ATL-I). Through MTT assay and morphology observation, we found cytotoxic effect of ATL-I in human K562 chronic myeloblastic leukemia (CML), U937 acute myeloblastic leukemia (AML) and Jurkat T lymphoma cells. In addition, ATL-I-induced apoptosis was demonstrated by sub G1 and fragmented chromosomal DNA detection using flow cytometry, enzyme-linked immunosorbent assay (ELISA) and agarose electrophoresis. Finally, we found ATL-I also induced caspase-3 and caspase-9 activation through the detection of procaspase-3, procaspase-9 and caspase-3 substrate poly(ADP-ribose) polymerase (PARP) by immunoblotting. Interestingly, we found that ATL-I induced not only apoptosis but also differentiation, as upregulation of CD14 and CD68 surface markers and increase of phagocytosis ability were discovered in ATL-I-treated K562 CML and U937 AML cells. Our study thus suggests the potential of developing new leukemia therapies by using ATL-I for leukemia treatment in the future.