Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia
Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia
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大麻二醇直接靶向线粒体并干扰急性淋巴细胞白血病的钙稳态
DOI：
10.1038/s41419-019-2024-0
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发表时间：
2019-10-14
影响因子：
9
通讯作者：
Dobrovinskaya, Oxana
中科院分区：
文献类型：
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作者：
Olivas-Aguirre, Miguel;Torres-Lopez, Liliana;Dobrovinskaya, Oxana
非精神活性大麻素大麻二醇(CBD)的抗癌特性已在不同组织来源的肿瘤上得到证实。CBD的不同分子靶点包括大麻素受体和一些质膜离子通道。在这里，我们已经证明了来自T系急性淋巴细胞白血病(T-ALL)的细胞系，但不是静止的健康T细胞，对CBD治疗高度敏感。CBD效应不依赖于大麻素受体或质膜钙离子通透通道。相反，CBD直接针对线粒体并改变其处理钙离子的能力。在致死浓度下，CBD导致线粒体钙超载，稳定的线粒体过渡孔洞形成和细胞死亡。我们的结果表明，CBD是一个有吸引力的候选方案，可纳入T-ALL的化疗方案。
Anticancer properties of non-psychoactive cannabinoid cannabidiol (CBD) have been demonstrated on tumors of different histogenesis. Different molecular targets for CBD were proposed, including cannabinoid receptors and some plasma membrane ion channels. Here we have shown that cell lines derived from acute lymphoblastic leukemia of T lineage (T-ALL), but not resting healthy T cells, are highly sensitive to CBD treatment. CBD effect does not depend on cannabinoid receptors or plasma membrane Ca2+-permeable channels. Instead, CBD directly targets mitochondria and alters their capacity to handle Ca2+. At lethal concentrations, CBD causes mitochondrial Ca2+ overload, stable mitochondrial transition pore formation and cell death. Our results suggest that CBD is an attractive candidate to be included into chemotherapeutic protocols for T-ALL treatment.