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褐藻来源的昆布多糖通过线粒体功能障碍和内质网应激抑制卵巢癌细胞的生长。

Laminarin-Derived from Brown Algae Suppresses the Growth of Ovarian Cancer Cells via Mitochondrial Dysfunction and ER Stress.

机构信息

Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

出版信息

Mar Drugs. 2020 Mar 9;18(3):152. doi: 10.3390/md18030152.

Abstract

Ovarian cancer (OC) is difficult to diagnose at an early stage and leads to the high mortality rate reported in the United States. Standard treatment for OC includes maximal cytoreductive surgery followed by platinum-based chemotherapy. However, relapse due to chemoresistance is common in advanced OC patients. Therefore, it is necessary to develop new anticancer drugs to suppress OC progression. Recently, the anticancer effects of laminarin, a beta-1,3-glucan derived from brown algae, have been reported in hepatocellular carcinoma, colon cancer, leukemia, and melanoma. However, its effects in OC are not reported. We confirmed that laminarin decreases cell growth and cell cycle progression of OC cells through the regulation of intracellular signaling. Moreover, laminarin induced cell death through DNA fragmentation, reactive oxygen species generation, induction of apoptotic signals and endoplasmic reticulum (ER) stress, regulation of calcium levels, and alteration of the ER-mitochondria axis. Laminarin was not cytotoxic in a zebrafish model, while in a zebrafish xenograft model, it inhibited OC cell growth. These results suggest that laminarin may be successfully used as a novel OC suppressor.

摘要

卵巢癌(OC)在早期诊断困难,导致美国报道的高死亡率。OC 的标准治疗包括最大限度的细胞减灭术,然后进行铂类化疗。然而,晚期 OC 患者经常因化疗耐药而复发。因此,有必要开发新的抗癌药物来抑制 OC 的进展。最近,从褐藻中提取的β-1,3-葡聚糖岩藻聚糖的抗癌作用已在肝癌、结肠癌、白血病和黑色素瘤中得到报道。然而,其在 OC 中的作用尚未报道。我们通过调节细胞内信号证实,岩藻聚糖可降低 OC 细胞的生长和细胞周期进程。此外,岩藻聚糖通过 DNA 片段化、活性氧生成、诱导凋亡信号和内质网(ER)应激、钙水平调节以及 ER-线粒体轴的改变诱导细胞死亡。岩藻聚糖在斑马鱼模型中没有细胞毒性,而在斑马鱼异种移植模型中,它抑制了 OC 细胞的生长。这些结果表明,岩藻聚糖可能成功地用作新型 OC 抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8442/7143329/c0551cae8d7a/marinedrugs-18-00152-g001.jpg

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