The Anti-Metastatic Action of Oxyresveratrol via Suppression of Phosphoryl-ERK/-PKCα-Mediated Sp1/MMP1 Signaling in Human Renal Carcinoma Cells

IF 4.4 3区医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-08-22 DOI:10.1002/tox.24400

Tsai-Kun Wu, Yi-Hsien Hsieh, Tung-Wei Hung, Yi-Chen Lin, Chia-Liang Lin, Yu-Jou Liu, Ying-Ru Pan, Jen-Pi Tsai

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Abstract

Oxyresveratrol (OxyR) exerts biological and pharmacological effects in a variety of tumor cells, including antioxidant action, antitumor activity, and proapoptotic effects. However, the regulation of targeted signaling pathways by OxyR and the mechanism underlying these effects in human renal cell carcinoma (RCC) have been less studied. We observed that OxyR at noncytotoxic doses did not affect the growth of human RCC cells or normal kidney HK2 cells. OxyR inhibited ACHN and Caki-1 cell migration and invasion through targeting matrix metalloproteinase 1 (MMP1) expression. Analysis of clinical databases showed that high MMP1 expression is associated with lower overall survival (OS) in these cancers (p < 0.01). OxyR significantly inhibited the mRNA and protein expression of Sp1. Furthermore, luciferase assay results showed that OxyR inhibited Sp1 transcriptional activity. Additionally, OxyR preferentially suppressed the activation of ERK and PKCα. Treatment with U0126 (MEK inhibitor) or G06976 (PKCα inhibitor) clearly decreased Sp1 and MMP1 expression and inhibited RCC cell migration and invasion. In conclusion, OxyR may be a potential antitumor therapy for the inhibition of migration and invasion by controlling p-ERK/Sp1 and p-PKCα/Sp1-mediated MMP1 expression in RCC.

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活氧白藜芦醇通过抑制磷酰-ERK/-PKCα介导的人肾癌细胞 Sp1/MMP1 信号转导而发挥抗转移作用

氧基白藜芦醇（OxyR）可对多种肿瘤细胞产生生物和药理作用，包括抗氧化作用、抗肿瘤活性和促凋亡作用。然而，对于氧白藜芦醇在人类肾细胞癌（RCC）中对靶向信号通路的调控及其作用机制的研究较少。我们观察到，非细胞毒性剂量的 OxyR 不会影响人类 RCC 细胞或正常肾脏 HK2 细胞的生长。OxyR通过靶向基质金属蛋白酶1（MMP1）的表达，抑制了ACHN和Caki-1细胞的迁移和侵袭。对临床数据库的分析表明，MMP1的高表达与这些癌症较低的总生存率（OS）有关（p

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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.