Department of Radiation Oncology, Samsung Medical Center, Seoul, 06351, South Korea.
Marine Natural Product Chemistry Laboratory, Korea Institute of Ocean Science, and Technology, Ansan, 426-744, South Korea.
Sci Rep. 2018 Apr 20;8(1):6317. doi: 10.1038/s41598-018-24745-w.
Although radiation therapy is an effective treatment modality in many cancers, there is an urgent need to develop therapeutic drugs capable of overcoming radioresistance or minimizing normal tissue toxicity. A wide variety of marine-derived bioactive compounds have been screened for anti-cancer drug discovery, but little is known regarding radiation therapy applications. In this study, six different extracts of marine sponges collected from the Micronesian sea were screened for anti-cancer and radiosensitizing activity. Two extracts derived from Agelas sponges collected off the coast of Kosrae and Chuuk, the Federated States of Micronesia significantly decreased clonogenic survival of hepatocellular carcinoma (HCC) cells after exposure to ionizing radiation (IR). The Agelas extracts augmented IR-induced apoptosis and accumulation of reactive oxygen species (ROS). Endoplasmic reticulum (ER) stress was increased via unfolded protein response stimulation, which induced autophagy. N-acetylcysteine, a ROS scavenger, diminished ER stress and autophagy induction effects. This result indicated that Agelas extracts may sensitize HCC cells to IR via ROS overproduction in vitro. Our findings suggest that the Agelas sp. may have potential utility in radiosensitizer development.
尽管放射疗法在许多癌症的治疗中是一种有效的方法，但迫切需要开发能够克服放射抗性或最小化正常组织毒性的治疗药物。已经筛选了各种各样的海洋来源的生物活性化合物来寻找抗癌药物，但对于放射治疗的应用知之甚少。在这项研究中，从密克罗尼西亚海域采集的六种不同的海绵提取物被筛选出具有抗癌和放射增敏活性。两种从科斯雷和楚克，密克罗尼西亚联邦采集的水螅海绵提取物在暴露于电离辐射（IR）后显著降低了肝癌（HCC）细胞的集落形成存活率。Agelas 提取物增强了 IR 诱导的细胞凋亡和活性氧（ROS）的积累。通过未折叠蛋白反应刺激增加内质网（ER）应激，从而诱导自噬。ROS 清除剂 N-乙酰半胱氨酸减弱了 ER 应激和自噬诱导作用。这一结果表明，Agelas 提取物可能通过体外产生过多的 ROS 使 HCC 细胞对 IR 敏感。我们的研究结果表明，Agelas sp. 可能在放射增敏剂的开发中具有潜在的用途。
