Differential contribution of ROS to resveratrol-induced cell death and loss of self-renewal capacity of ovarian cancer stem cells.

Differential contribution of ROS to resveratrol-induced cell death and loss of self-renewal capacity of ovarian cancer stem cells.
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DOI:
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发表时间:
2015
影响因子:
2
通讯作者:
Manabu Seino;M. Okada;Keita Shibuya;Shizuka Seino;Shuhei Suzuki;Hiroyuki Takeda;T. Ohta;H. Kurachi;C. Kitanaka
Manabu Seino;M. Okada;Keita Shibuya;Shizuka Seino;Shuhei Suzuki;Hiroyuki Takeda;T. Ohta;H. Kurachi;C. Kitanaka
中科院分区:
医学4区
文献类型:
--
作者:
Manabu Seino;M. Okada;Keita Shibuya;Shizuka Seino;Shuhei Suzuki;Hiroyuki Takeda;T. Ohta;H. Kurachi;C. Kitanaka

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背景/目的肿瘤干细胞(cancer stem cells,CSCs)被认为是卵巢癌预后不良的主要原因之一。因此,确定通过诱导细胞死亡和/或自我更新能力丧失来消除卵巢CSC的有效措施将是成功管理卵巢癌的关键。材料与方法检测白藜芦醇对A2780人卵巢癌细胞CSCs活力和自我更新能力的影响。活性氧(ROS)的参与也进行了研究。结果在对正常人成纤维细胞无毒的浓度下,白藜芦醇独立于ROS有效地杀死卵巢CSCs,而ROS依赖性地损害了白藜芦醇处理后存活的卵巢CSCs的自我更新能力。结论我们的研究结果不仅揭示了白藜芦醇的一种新的作用机制,而且表明白藜芦醇或其类似物可能有助于CSC对卵巢癌的治疗。
BACKGROUND/AIM Cancer stem cells (CSCs) are considered to contribute to the poor prognosis of ovarian cancer as a major cause of fatal recurrence. Identification of effective measures to eliminate ovarian CSCs through induction of cell death and/or loss of self-renewal capacity would, therefore, be key to successful management of ovarian cancer. MATERIALS AND METHODS The effects of resveratrol on the viability and self-renewal capacity of CSCs derived from A2780 human ovarian cancer cells were examined. The involvement of reactive oxygen species (ROS) was also investigated. RESULTS At a non-toxic to normal human fibroblasts concentration, resveratrol effectively killed ovarian CSCs independently of ROS, while ROS-dependently impaired the self-renewal capacity of ovarian CSCs that survived resveratrol treatment. CONCLUSION Our findings not only shed light on a novel mechanism of action for resveratrol but also suggest that resveratrol, or its analogs, may be useful for CSC-directed therapy against ovarian cancer.