Gossypol Inhibits Metastasis of Lung Cell Carcinoma by Reversing Epithelial to Mesenchymal Transition and Suppressing Proteases Activity

IF 4.4 3区医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-09-12 DOI:10.1002/tox.24363

Yih-Shou Hsieh, Ching-Han Yu, Shu-Chen Chu, Chin-Yin Lin, Pei-Ni Chen

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Abstract

Gossypol, a natural polyphenolic compound, possesses antivirus activity and induces cell death of different types of tumors. However, the efficacy of gossypol on lung carcinoma metastases and epithelial to mesenchymal transition remains unknown. The aim of the present work was to determine the cellular and molecular mechanism of the anti-cancer and anti-metastatic efficacies of gossypol on human lung carcinoma cells. Gossypol showed a marked suppression of the viability, motility, and invasion in H1299 and A549 cells. Zymography assay showed that gossypol was sufficient to suppress the activities of urokinase-type plasminogen activator and matrix metalloproteinase-2. Gossypol reversed TGF-β-induced epithelial to mesenchymal transition. Gossypol reduced vimentin, p-FAK, p-Src and p-paxillin. In vivo studies of gossypol were performed using subcutaneous inoculation and tail vein injection of A549 into immunodeficient BALB/c nude mice and severe combined immunodeficient mice.

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棉酚通过逆转上皮到间质转化和抑制蛋白酶活性抑制肺细胞癌转移

棉酚是一种天然多酚化合物，具有抗病毒活性，可诱导不同类型肿瘤的细胞死亡。然而，棉酚对肺癌转移和上皮细胞向间质转化的疗效仍然未知。本研究旨在确定棉酚对人类肺癌细胞抗癌和抗转移功效的细胞和分子机制。棉酚对 H1299 和 A549 细胞的活力、运动性和侵袭性有明显的抑制作用。酶谱分析显示，棉酚足以抑制尿激酶型纤溶酶原激活剂和基质金属蛋白酶-2的活性。棉酚能逆转 TGF-β 诱导的上皮向间充质转化。苔酚可减少波形蛋白、p-FAK、p-Src 和 p-paxillin。通过皮下注射和尾静脉注射 A549 到免疫缺陷 BALB/c 裸鼠和严重联合免疫缺陷小鼠体内，对棉酚进行了体内研究。

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来源期刊

Environmental Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

8.90%

发文量

261

审稿时长

4.5 months

期刊介绍： The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.