Plasma-stimulated medium kills TRAIL-resistant human malignant cells by promoting caspase-independent cell death via membrane potential and calcium dynamics modulation.
Plasma-stimulated medium kills TRAIL-resistant human malignant cells by promoting caspase-independent cell death via membrane potential and calcium dynamics modulation.
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DOI：
10.3892/ijo.2018.4251
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发表时间：
2018-03
影响因子：
5.2
通讯作者：
Suzuki-Karasaki Y
中科院分区：
文献类型：
--
作者：
Tokunaga T;Ando T;Suzuki-Karasaki M;Ito T;Onoe-Takahashi A;Ochiai T;Soma M;Suzuki-Karasaki Y
肿瘤坏死因子相关凋亡诱导配体（TRAIL）和冷等离子体刺激培养基（PSM）已被证明具有肿瘤选择性细胞毒性，并已成为癌症治疗的有前途的新工具。然而，迄今为止，至少就我们所知，没有数据表明哪种物质在杀死癌细胞方面更有效。因此，在这项研究中，我们系统地比较了它们杀死不同来源的人类恶性细胞的能力。我们发现，PSM剂量依赖性地杀死TRAIL抗性黑色素瘤、骨肉瘤和神经母细胞瘤细胞。PSM对成骨细胞的细胞毒性较小。PSM在诱导caspase-3/7活化、线粒体网络畸变和caspase非依赖性细胞死亡方面比TRAIL更有效。我们还发现，PSM更有效地诱导质膜去极化（PMD）和破坏内质网-线粒体Ca 2+稳态。此外，持续性PMD是由不同的膜去极化剂引起的;单独使用抗II型糖尿病药物格列本脲会引起线粒体碎片化，并增强TRAIL诱导的Ca 2+调节、线粒体网络异常和半胱天冬酶非依赖性细胞杀伤。这些结果表明，PSM具有优于TRAIL的治疗优势，这是由于PSM通过破坏膜电位和Ca 2+稳态通过线粒体网络畸变引起半胱天冬酶非依赖性细胞死亡的能力更强。这些发现可能为开发PSM作为治疗TRAIL耐药恶性细胞的新方法提供了强有力的理论基础。
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cold plasma-stimulated medium (PSM) have been shown to exhibit tumor-selective cytotoxicity and have emerged as promising new tools for cancer treatment. However, to date, at least to the best of our knowledge, no data are available as to which substance is more potent in killing cancer cells. Thus, in this study, we systematically compared their abilities to kill human malignant cells from different origins. We found that PSM dose-dependently killed TRAIL-resistant melanoma, osteosarcoma and neuroblastoma cells. Moreover, PSM had little cytotoxicity toward osteoblasts. PSM was more potent than TRAIL in inducing caspase-3/7 activation, mitochondrial network aberration and caspase-independent cell death. We also found that PSM was more potent in inducing plasma membrane depolarization (PMD) and disrupting endoplasmic-mitochondrial Ca2+ homeostasis. Moreover, persistent PMD was caused by different membrane-depolarizing agents; the use of the anti-type II diabetes drug, glibenclamide, alone caused mitochondrial fragmentation and enhanced TRAIL-induced Ca2+ modulation, mitochondrial network abnormalities and caspase-independent cell killing. These results demonstrate that PSM has a therapeutic advantage over TRAIL owing to its greater capacity to evoke caspase-independent cell death via mitochondrial network aberration by disrupting membrane potential and Ca2+ homeostasis. These findings may provide a strong rationale for developing PSM as a novel approach for the treatment of TRAIL-resistant malignant cells.
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影响因子：
3.6
作者：
Kalal BS;Upadhya D;Pai VR
通讯作者：
Pai VR
影响因子：
8
作者：
Dimberg LY;Anderson CK;Camidge R;Behbakht K;Thorburn A;Ford HL
通讯作者：
Ford HL
影响因子：
5.2
作者：
Akita, Mamoru;Suzuki-Karasaki, Miki;Suzuki-Karasaki, Yoshihiro
通讯作者：
Suzuki-Karasaki, Yoshihiro
影响因子：
6.4
作者：
Ishaq, Musarat;Evans, Margaret (Meg);Ostrikov, Kostya (Ken)
通讯作者：
Ostrikov, Kostya (Ken)
骨肉瘤化疗耐药的分子机制（综述）。
影响因子：
2.9
作者：
He H;Ni J;Huang J
通讯作者：
Huang J