Pentacyclic triterpenoid ursolic acid induces apoptosis with mitochondrial dysfunction in adult T-cell leukemia MT-4 cells to promote surrounding cell growth
Pentacyclic triterpenoid ursolic acid induces apoptosis with mitochondrial dysfunction in adult T-cell leukemia MT-4 cells to promote surrounding cell growth
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DOI：
10.1007/s12032-022-01707-x
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发表时间：
2022-06-08
期刊：
影响因子：
3.4
通讯作者：
Yoshida, Yasuhiro
中科院分区：
文献类型：
--
作者：
Shen, Mengyue;Wang, Duo;Yoshida, Yasuhiro
研究齐墩果酸（OA）和熊果酸（UA）对成人t细胞白血病细胞的抗肿瘤作用。OA和UA剂量依赖性地抑制成人t细胞白血病细胞的增殖。ua处理的细胞显示caspase 3/7和caspase 9活化。在ua处理的MT-4细胞中检测到PARP切割。UA可抑制mTOR和PDK-1的激活。电镜下观察UA处理后MT-4细胞的自噬体。在共聚焦显微镜下，OA和ua处理的MT-4细胞中观察到线粒体自噬。UA处理后，MT-4细胞线粒体膜电位明显降低，线粒体呼吸和有氧糖酵解明显减少。此外，根据线粒体膜电位将MT-1和MT-4细胞分为两个区域。经ua处理的MT-4细胞均表现出caspase 3/7的高活化，而Z-vad抑制了该活性。有趣的是，MT-4细胞与经过筛选的ua处理的细胞共培养显示出增强的增殖。最后，UA诱导成人t细胞白血病患者外周血单个核细胞的细胞死亡和体外PARP裂解。因此，ua处理的MT-4细胞在线粒体功能障碍后显示caspase激活，并可能向周围细胞产生生存信号。
We investigated the antitumor effects of oleanolic acid (OA) and ursolic acid (UA) on adult T-cell leukemia cells. OA and UA dose-dependently inhibited the proliferation of adult T-cell leukemia cells. UA-treated cells showed caspase 3/7 and caspase 9 activation. PARP cleavage was detected in UA-treated MT-4 cells. Activation of mTOR and PDK-1 was inhibited by UA. Autophagosomes were detected in MT-4 cells after UA treatment using electron microscopy. Consistently, mitophagy was observed in OA- and UA-treated MT-4 cells by confocal microscopy. The mitochondrial membrane potential in MT-4 cells considerably decreased, and mitochondrial respiration and aerobic glycolysis were significantly reduced following UA treatment. Furthermore, MT-1 and MT-4 cells were sorted into two regions based on their mitochondrial membrane potential. UA-treated MT-4 cells from both regions showed high activation of caspase 3/7, which were inhibited by Z-vad. Interestingly, MT-4 cells cocultured with sorted UA-treated cells showed enhanced proliferation. Finally, UA induced cell death and ex vivo PARP cleavage in peripheral blood mononuclear cells from patients with adult T-cell leukemia. Therefore, UA-treated MT-4 cells show caspase activation following mitochondrial dysfunction and may produce survival signals to the surrounding cells.
影响因子：
2.9
作者：
Kimura R;Mori N
通讯作者：
Mori N