Kuramoto Kenta, Suzuki Shuhei, Sakaki Hirotsugu, Takeda Hiroyuki, Sanomachi Tomomi, Seino Shizuka, Narita Yoshitaka, Kayama Takamasa, Kitanaka Chifumi, Okada Masashi
Department of Molecular Cancer Science Yamagata University School of Medicine Japan.
Department of Clinical Oncology Yamagata University School of Medicine Japan.
FEBS Open Bio. 2017 May 8;7(6):835-844. doi: 10.1002/2211-5463.12226. eCollection 2017 Jun.
Glioblastoma multiforme is the most malignant primary intrinsic brain tumor. Glioma stem cells (GSCs) are associated with chemoradiotherapy resistance and the recurrence of glioblastomas after conventional therapy. The targeting of GSCs is potentially an effective treatment for the long-term survival of glioblastoma patients. Licochalcone A, a natural chalconoid from licorice root, exerts anticancer effects; however, its effect on GSCs remains unknown. We found that Licochalcone A induced massive caspase-dependent death in GSCs but not in differentiated GSCs nor normal somatic and neural stem cells. Prior to cell death, Licochalcone A caused mitochondrial fragmentation and reduced the membrane potential and ATP production in GSCs. Thus, Licochalcone A induces mitochondrial dysfunction and shows promise as an anticancer stem cell drug.
多形性胶质母细胞瘤是最恶性的原发性脑内肿瘤。胶质瘤干细胞(GSCs)与放化疗耐药以及胶质母细胞瘤在传统治疗后的复发相关。靶向GSCs可能是胶质母细胞瘤患者长期生存的有效治疗方法。甘草查尔酮A是一种从甘草根中提取的天然查耳酮,具有抗癌作用;然而,其对GSCs的作用尚不清楚。我们发现甘草查尔酮A在GSCs中诱导大量半胱天冬酶依赖性死亡,但在分化的GSCs以及正常体细胞和神经干细胞中未诱导死亡。在细胞死亡之前,甘草查尔酮A导致线粒体碎片化,并降低了GSCs中的膜电位和ATP生成。因此,甘草查尔酮A诱导线粒体功能障碍,有望成为一种抗癌干细胞药物。