异连蛋白通过抑制 CXC 趋化因子受体 4 的表达抑制乳腺癌和结肠癌细胞的侵袭

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Biomolecules & Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-10-07 DOI:10.4062/biomolther.2024.137
Buyun Kim, Byoungduck Park
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引用次数: 0

摘要

癌症转移仍占癌症相关死亡的 90%,但转移的分子机制尚不清楚。一些趋化因子及其受体介导了肿瘤细胞的转移,特别是通过调节血管生成、肿瘤细胞增殖和凋亡的长期效应。其中,CXC 趋化因子受体 4(CXCR4)已被证明通过与配体(CXCL12)(又称基质细胞衍生因子 1α(SDF-1α))相互作用,在癌症转移中发挥关键作用。CXCR4 启动子区域的特征非常明显,其表达受多种转录因子控制,包括 NF-κB、HIF-1α 等。异连翘素(ISO)是一种 3'、4'、5、7-四羟基-6-C-吡喃葡萄糖基黄酮。据报道,ISO 具有抗氧化、抗癌和抗炎特性。然而,ISO 在下调 CXCR4 后的抗转移作用尚不清楚,其抗肿瘤活性的机制也有待阐明。在本研究中,我们发现 ISO 通过 NF-κB 调节抑制了乳腺癌和结肠癌细胞中 CXCR4 的表达。我们还证明了 ISO 可抑制多种肿瘤细胞中 CXCR4 的表达。此外,我们还发现 CXCR4 的表达是通过抑制转录过程来调节的。抑制 CXCR4 的表达还能减少 CXCL12 对癌细胞的侵袭。总之,我们的研究结果表明,ISO 是一种新型的抑制剂,可以调节 CXCR4 的表达,是促进抗肿瘤活性的关键分子。
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Isoorientin Suppresses Invasion of Breast and Colon Cancer Cells by Inhibition of CXC Chemokine Receptor 4 Expression.

Cancer metastasis still accounts for up to 90% of cancer-related deaths, but the molecular mechanism for metastasis is unclear. Several chemokines and their receptors mediate tumor cell metastasis, particularly through long-term effects that regulate angiogenesis, tumor cell proliferation and apoptosis. Among them, CXC chemokine receptor 4 (CXCR4) has been shown to play a pivotal role in cancer metastasis through interaction with a ligand (CXCL12), also known as stromal cell-derived factor 1α (SDF-1α). The CXCR4 promoter region is well characterized, and its expression is controlled by various transcriptional factors, including NF-κB, HIF-1α, and so forth. Isoorientin (ISO) is a 3', 4', 5, 7-tetrahydroxy-6-C-glucopyranosyl flavone. ISO has been reported to exhibit anti-oxidant, anti-cancer, and anti-inflammatory properties. However, the anti-metastatic effect of ISO following downregulation of CXCR4 is unknown, and the mechanism underlying the antitumor activity has yet to be elucidated. In our present study, we showed that ISO inhibited the expression of CXCR4 through NF-κB regulation in breast and colon cancer cells. We have also demonstrated that ISO inhibits CXCR4 expression in a variety of tumor cells. Furthermore, we found that CXCR4 expression is regulated through inhibition of the transcription process. Inhibition of CXCR4 expression also reduced the invasion of cancer cells by CXCL12. In conclusion, our results suggest that ISO is a novel inhibitor to regulate CXCR4 expression and the key molecule contributing to antitumor activity.

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来源期刊
CiteScore
6.60
自引率
8.10%
发文量
72
审稿时长
6-12 weeks
期刊介绍: Biomolecules & Therapeutics (Biomolecules & Therapeutics) (Print ISSN 1976-9148, Online ISSN 2005-4483) is an international, peer-reviewed, open access journal that covers pharmacological and toxicological fields related to bioactive molecules and therapeutics. It was launched in 1993 as "The Journal of Applied Pharmacology (ISSN 1225-6110)", and renamed "Biomolecules & Therapeutics" (Biomol Ther: abbreviated form) in 2008 (Volume 16, No. 1). It is published bimonthly in January, March, May, July, September and November. All manuscripts should be creative, informative, and contribute to the development of new drugs. Articles in the following categories are published: review articles and research articles.
期刊最新文献
Isoorientin Suppresses Invasion of Breast and Colon Cancer Cells by Inhibition of CXC Chemokine Receptor 4 Expression. Jolkinolide B Ameliorates Liver Inflammation and Lipogenesis by Regulating JAK/STAT3 Pathway. Phytotherapeutic BS012 and Its Active Component Ameliorate Allergic Asthma via Inhibition of Th2-Mediated Immune Response and Apoptosis. Regulatory Mechanisms Governing the Autophagy-Initiating VPS34 Complex and Its inhibitors. Translation Initiation Factor-2S2 (eIF2S2) Contributes to Cervical Carcinogenesis by Inhibiting the TGF-β/SMAD4 Signaling Pathway.
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