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海洋生物活性化合物二酮诱导人胰腺癌细胞 PANC-1 凋亡并抑制其生长。

Marine bioactive compound dieckol induces apoptosis and inhibits the growth of human pancreatic cancer cells PANC-1.

机构信息

Department of Pancreatic Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Departments of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

出版信息

J Biochem Mol Toxicol. 2021 Feb;35(2):e22648. doi: 10.1002/jbt.22648. Epub 2020 Oct 14.

DOI:10.1002/jbt.22648
PMID:33051972
Abstract

Pancreatic cancer, which threatens the global population, is a very aggressive disease with an increased mortality rate. Regarding the types of cancer, pancreatic cancer is prone to display significant resistance to conventional therapy, therefore there 5-year survival rate is only 2% to 9%. Bioactive metabolites of marine algae such as polysaccharides, chitin, carternoids, and sterols possess immense pharmacological properties and tend to be promising alternatives for cancer treatment. Dieckol is one such polyphenolic bioactive compound extracted from brown algae Ecklonia cava, which is proven to possess antioxidant, anti-inflammatory, antibacterial, antidiabetic properties. Therefore in the present study, we analyzed the anticancer property of dieckol on PANC-1 pancreatic carcinoma cells. The cytotoxicity property of dieckol against PANC-1 cells was assessed with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, and cell morphological analysis. The generation of reactive oxygen species by dieckol on PANC-1 was analyzed with DCFH-DA staining and confirmed by quantifying antioxidants levels in untreated and dieckol-treated PANC-1 cells. The induction of apoptosis was further evaluated with different staining techniques such as Rhodamine 123 staining, acridine orange/ethidium bromide staining, DAPI staining, propidium iodide staining and was confirmed by estimating the protein expression of apoptotic genes, Bax and Bcl2. Cell adhesion assay and estimation of inflammatory cytokines were performed to detect the inhibitory effect of dieckol against cancer cell progression. It is further confirmed by analyzing cancer cell progression proteins, that is, proliferating cell nuclear antigen and cyclin D1 expressions in untreated and dieckol-treated PANC-1 cells. Our overall results authentically prove dieckol persuasively induces apoptosis and inhibits the progression of human pancreatic cancer cells in vitro, suggesting dieckol as a potent marine-based phytochemical to treat pancreatic cancer.

摘要

胰腺癌威胁着全球人口,是一种非常侵袭性的疾病,死亡率较高。在癌症类型方面,胰腺癌容易对常规治疗产生显著耐药性,因此 5 年生存率仅为 2%至 9%。海洋藻类的生物活性代谢产物,如多糖、几丁质、类胡萝卜素和固醇,具有巨大的药理特性,有望成为癌症治疗的替代方法。二酮是从褐藻裙带菜中提取的一种多酚类生物活性化合物,已被证明具有抗氧化、抗炎、抗菌、抗糖尿病的特性。因此,在本研究中,我们分析了二酮对 PANC-1 胰腺癌细胞的抗癌特性。用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐测定法和细胞形态分析评估二酮对 PANC-1 细胞的细胞毒性。用 DCFH-DA 染色分析二酮在 PANC-1 中产生的活性氧,并通过定量未处理和二酮处理的 PANC-1 细胞中的抗氧化剂水平来确认。通过不同的染色技术,如罗丹明 123 染色、吖啶橙/溴化乙锭染色、DAPI 染色、碘化丙啶染色进一步评估细胞凋亡,并通过估计凋亡基因 Bax 和 Bcl2 的蛋白表达来确认。进行细胞黏附测定和炎症细胞因子的估计,以检测二酮对癌细胞进展的抑制作用。通过分析未处理和二酮处理的 PANC-1 细胞中增殖细胞核抗原和细胞周期蛋白 D1 的蛋白表达,进一步证实了这一点。我们的整体结果真实地证明了二酮能够在体外有效地诱导人胰腺癌细胞凋亡并抑制其进展,表明二酮作为一种有效的海洋植物化学物质,可用于治疗胰腺癌。

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