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https://ir.csmu.edu.tw:8080/ir/handle/310902500/24598
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Title: | The Curcumin Analogue, EF-24, Triggers p38 MAPK-Mediated Apoptotic Cell Death via Inducing PP2A-Modulated ERK Deactivation in Human Acute Myeloid Leukemia Cells |
Authors: | Hsiao, PC;Chang, JH;Lee, WJ;Ku, CC;Tsai, MY;Yang, SF;Chien, MH |
Keywords: | acute myeloid leukemia;apoptosis;EF-24;protein phosphatase 2 a;p38 mitogen-activated protein kinase;extracellular-regulated protein kinase |
Date: | 2020 |
Issue Date: | 2022-08-09T08:04:58Z (UTC)
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Publisher: | MDPI |
Abstract: | Curcumin (CUR) has a range of therapeutic benefits against cancers, but its poor solubility and low bioavailability limit its clinical use. Demethoxycurcumin (DMC) and diphenyl difluoroketone (EF-24) are natural and synthetic curcumin analogues, respectively, with better solubilities and higher anti-carcinogenic activities in various solid tumors than CUR. However, the efficacy of these analogues against non-solid tumors, particularly in acute myeloid leukemia (AML), has not been fully investigated. Herein, we observed that both DMC and EF-24 significantly decrease the proportion of viable AML cells including HL-60, U937, and MV4-11, harboring different NRAS and Fms-like tyrosine kinase 3 (FLT3) statuses, and that EF-24 has a lower half maximal inhibitory concentration (IC50) than DMC. We found that EF-24 treatment induces several features of apoptosis, including an increase in the sub-G(1)population, phosphatidylserine (PS) externalization, and significant activation of extrinsic proapoptotic signaling such as caspase-8 and -3 activation. Mechanistically, p38 mitogen-activated protein kinase (MAPK) activation is critical for EF-24-triggered apoptosis via activating protein phosphatase 2A (PP2A) to attenuate extracellular-regulated protein kinase (ERK) activities in HL-60 AML cells. In the clinic, patients with AML expressing high level of PP2A have the most favorable prognoses compared to various solid tumors. Taken together, our results indicate that EF-24 is a potential therapeutic agent for treating AML, especially for cancer types that lose the function of the PP2A tumor suppressor. |
URI: | http://dx.doi.org/10.3390/cancers12082163 https://www.webofscience.com/wos/woscc/full-record/WOS:000578882800001 https://ir.csmu.edu.tw:8080/handle/310902500/24598 |
Relation: | CANCERS ,2020 ,v12 ,issue 8 |
Appears in Collections: | [中山醫學大學研究成果] 期刊論文
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