Sulfated galactofucan from Sargassum thunbergii induces senescence in human lung cancer A549 cells
Sulfated galactofucan from Sargassum thunbergii induces senescence in human lung cancer A549 cells
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来自马尾藻的硫酸化半乳岩藻聚糖诱导人肺癌 A549 细胞衰老
DOI：
10.1039/d0fo00699h
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发表时间：
2020-05-01
期刊：
影响因子：
6.1
通讯作者：
Mao, Genxiang
中科院分区：
文献类型：
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作者：
Bao, Yizhong;He, Xinyue;Mao, Genxiang
从鼠尾藻（Sargassumthunbercium，S. Thunbertine）显示出多种生物活性，包括抗癌活性。在这项研究中，我们研究了硫酸化半乳糖藻聚糖（SWZ-4-H），这是成功地从S。目的：研究雷公藤多甙对人肺癌A549细胞生长的影响，探讨雷公藤多甙对人肺癌A549细胞生长的作用机制。体外实验表明，SWZ-4-H以剂量依赖性方式抑制细胞生长和数量（与对照相比，P < 0.05）。此外，用SWZ-4-H处理的细胞具有不规则的形态，包括增加的细胞体积和大的核，这表明衰老样变化。此外，SWZ-4-H以剂量依赖性方式增加衰老相关的β-半乳糖苷酶（SA-β-Gal）染色;然而，虽然较低浓度（1 mg mL（-1））主要诱导衰老而不引起细胞死亡，但较高剂量（3 mg mL（-1））诱导衰老和细胞死亡。通过分析p53、p21、p16和Rb（p-RB）的表达进一步证实了SWZ-4-H的作用; SWZ-4-H以剂量依赖性方式显著增加p53、p21和p16的表达，并降低磷酸化Rb（p-RB）。此外，体内实验表明，SWZ-4-H显着减少肿瘤体积，而不影响体重。综上所述，我们的研究结果表明SWZ-4-H可以通过调控p53、p21、p16和p-Rb诱导肺癌细胞衰老，从而为SWZ-4-H在人肺癌A549细胞中的抗癌机制提供了新的视角。
Isolated compounds from Sargassum thunbergii (S. thunbergii) have shown to exhibit diverse biological activities, including anti-cancer activity. In this study, we examined the effect of sulfated galactofucan (SWZ-4-H), which was successfully isolated from S. thunbergii, and its underlying mechanism on human lung cancer (LC) A549 cell growth in vitro and in vivo. In vitro experiment indicated that SWZ-4-H decreased cell growth and number in a dose-dependent manner (P < 0.05 vs. control). Besides, cells treated with SWZ-4-H had irregular morphology, including increased cell volumes, and large nuclei, which suggested senescence-like changes. Moreover, SWZ-4-H increased senescence-related beta-galactosidase (SA-beta-Gal) staining in a dose-dependent manner; however, while lower (1 mg mL(-1)) concentration induced mainly senescence without causing cell death, higher dosage (3 mg mL(-1)) induced both senescence and cell death. The effect of SWZ-4-H was further confirmed by analyzing the expression of p53, p21, p16, and Rb (p-RB); SWZ-4-H significantly increased the expression of p53, p21, and p16 and decreased phosphorylated Rb (p-RB) in a dose-dependent manner. Moreover, in vivo experiment showed that SWZ-4-H significantly reduced the tumor volume without affecting the body weight. To sum up, our data indicated that SWZ-4-H could induce lung cancer senescence by regulating p53, p21, p16, and p-Rb, thus providing a novel perspective on anti-cancer mechanisms of SWZ-4-H in human lung cancer A549 cells.