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福斯汀通过 cAMP/PKA 依赖机制抑制黑色素瘤细胞生长。

Fustin suppressed melanoma cell growth via cAMP/PKA-dependent mechanism.

机构信息

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan.

出版信息

Biosci Biotechnol Biochem. 2024 Jul 22;88(8):900-907. doi: 10.1093/bbb/zbae072.

Abstract

Melanoma, a cancer arising from melanocytes, requires a novel treatment strategy because of the ineffectiveness of conventional therapies in certain patients. Fustin is a flavanonol found in young fustic (Cotinus coggygria). However, little is known about its antimelanoma effects. Our study demonstrates that fustin suppresses the growth of B16 melanoma cells. Phalloidin staining of cytoskeletal actin revealed that fustin induced a conformational change in the actin structure of melanoma cells, accompanied by suppressed phosphorylation of myosin regulatory light chain 2 (MLC2), a regulator of actin structure. Furthermore, the protein kinase A (cAMP-dependent protein kinase) inhibitor H89 completely attenuated fustin-induced downregulation of phosphorylated myosin phosphatase targeting subunit 1, which is involved in dephosphorylation of MLC2. In a mouse model, administration of fustin suppressed tumor growth in B16 melanoma cells without adverse effects. In conclusion, our findings suggest that fustin effectively suppresses melanoma cell growth both in vitro and in vivo.

摘要

黑素瘤是一种起源于黑素细胞的癌症,由于某些患者常规疗法无效,因此需要一种新的治疗策略。夫司停是存在于黄栌中的一种黄烷醇。然而,人们对其抗黑素瘤作用知之甚少。我们的研究表明,夫司停抑制 B16 黑素瘤细胞的生长。细胞骨架肌动蛋白的鬼笔环肽染色显示,夫司停诱导了黑素瘤细胞中肌动蛋白结构的构象变化,同时抑制了肌球蛋白调节轻链 2(MLC2)的磷酸化,MLC2 是肌动蛋白结构的调节剂。此外,蛋白激酶 A(cAMP 依赖性蛋白激酶)抑制剂 H89 完全减弱了夫司停诱导的磷酸化肌球蛋白磷酸酶靶向亚单位 1 的下调,该蛋白参与 MLC2 的去磷酸化。在小鼠模型中,夫司停的给药抑制了 B16 黑素瘤细胞的肿瘤生长,没有不良反应。总之,我们的研究结果表明,夫司停在体外和体内均能有效抑制黑素瘤细胞的生长。

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