Curcumin attenuates smoking and drinking activated NF-κB/IL-6 inflammatory signaling axis in cervical cancer.

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-10-20 DOI:10.1186/s12935-024-03513-z

Vivek K Kashyap, Prashanth K B Nagesh, Ajay K Singh, Andrew Massey, Godwin P Darkwah, Aaron George, Sheema Khan, Bilal B Hafeez, Nadeem Zafar, Santosh Kumar, Namita Sinha, Murali M Yallapu, Meena Jaggi, Subhash C Chauhan

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Abstract

Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation.

Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their cell migration and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay, and confocal microscopy. Herein, we used curcumin (Cur), and PLGA nanoparticle formulation of curcumin (PLGA-Cur) and determined effectiveness of free Cur and PLGA-Cur formulation on smoking and drinking activated NF-κB/IL-6 mediated inflammatory signaling pathways using in vitro cervical cancer models.

Results: Treatments with B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers in cervical cancer cells; it also enhanced migration and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGF. The molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by curcumin (Cur)/PLGA-Cur treatment.

Conclusions: These data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. In addition, attenuation of these effects by treatment with Cur/PLGA-Cur treatment, implies the role of curcumin in cervical cancer prevention and treatment.

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姜黄素可减轻吸烟和饮酒激活的宫颈癌NF-κB/IL-6炎症信号轴。

背景：众所周知，高危型人乳头瘤病毒可导致宫颈癌。多项临床研究强调，吸烟和饮酒是宫颈癌及其高级别前体的关键风险因素。在本研究中，我们调查了吸烟和/或饮酒是否会增强宫颈癌发生的分子机制，并确定了一种潜在的治疗方法来减轻其影响：方法：通过测量细胞迁移和侵袭特性的变化，评估了苯并[a]芘（B[a]P）和/或乙醇（EtOH）暴露对宫颈癌细胞的影响。使用 qRT-PCR、免疫印迹、ELISA、荧光素酶报告分析和共聚焦显微镜测定了 HPV16 E6/E7、NF-κB、细胞因子和炎症介质的表达。在此，我们使用姜黄素（Cur）和姜黄素的PLGA纳米颗粒制剂（PLGA-Cur），并利用体外宫颈癌模型确定游离姜黄素和PLGA-Cur制剂对吸烟和饮酒激活的NF-κB/IL-6介导的炎症信号通路的有效性：结果：B[a]P和/或EtOH能改变宫颈癌细胞中HPV16 E6/E7癌基因和EMT标记物的表达，还能增强迁移和侵袭。此外，B[a]P和/或EtOH暴露通过TNF-α和NF-κB信号促进炎症通路，导致IL-6上调和VEGF活化。姜黄素（Cur）/PLGA-Cur处理可有效减轻B[a]P和/或EtOH暴露引起的分子效应：这些数据表明，吸烟、饮酒和人乳头瘤病毒感染在宫颈癌发生过程中存在分子联系。此外，姜黄素/PLGA-Cur治疗可减轻这些影响，这意味着姜黄素在宫颈癌预防和治疗中的作用。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.