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.

中文翻译：

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海洋海绵Agelas sp。的放射增敏作用。自噬诱导肝癌细胞中的提取物。

尽管放射疗法在许多癌症中是一种有效的治疗方式，但迫切需要开发能够克服放射抗性或将正常组织毒性降至最低的治疗药物。已经筛选了多种海洋来源的生物活性化合物用于抗癌药物的发现，但是对于放射治疗的应用知之甚少。在这项研究中，对从密克罗尼西亚海中收集的六种不同的海用海绵提取物进行了抗癌和放射增敏活性筛选。暴露于电离辐射（IR）后，密克罗尼西亚联邦州科斯雷（Kosrae）和丘克（Chuuk）海岸附近采集的来自Agelas海绵的两种提取物显着降低了肝细胞癌（HCC）细胞的克隆形成存活率。Agelas提取物增强了IR诱导的细胞凋亡和活性氧（ROS）的积累。内质网（ER）应激通过未折叠的蛋白反应刺激而增加，这会引起自噬。N-乙酰半胱氨酸是一种ROS清除剂，可减少ER应激和自噬诱导作用。该结果表明，Agelas提取物可通过体外ROS过量生产使HCC细胞对IR敏感。我们的研究结果表明，Agelas sp。在放射增敏剂的开发中可能具有潜在的用途。我们的发现表明，Agelas sp。在放射增敏剂的开发中可能具有潜在的用途。我们的发现表明，Agelas sp。在放射增敏剂的开发中可能具有潜在的用途。