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阐明肉桂酰磺酰胺异羟肟酸的抗癌机制:来自鳞状细胞癌DNA含量分析和基因表达谱的见解

Elucidating the Anticancer Mechanisms of Cinnamoyl Sulfonamide Hydroxamate: Insights From DNA Content Analysis and Gene Expression Profiling in Squamous Cell Carcinoma.

作者信息

Cherian Eapen, Goyal Manoj, Mittal Neeti, Mathews Susan, Sagir Muhammad

机构信息

Oral and Maxillofacial Pathology, Travancore Dental College Medicity, Kollam, IND.

Oral and Maxillofacial Surgery, Santosh Deemed to Be University, Ghaziabad, IND.

出版信息

Cureus. 2024 Mar 30;16(3):e57236. doi: 10.7759/cureus.57236. eCollection 2024 Mar.

DOI:10.7759/cureus.57236
PMID:38686281
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11056768/
Abstract

BACKGROUND

Oral cancer is a major public health concern worldwide, with oral squamous cell carcinoma (OSCC) being one of its most common subtypes. Despite advances in diagnosis and management of this disease, there remains a need to develop new therapeutic approaches for better outcomes.

OBJECTIVE

This study aimed to investigate the molecular mechanisms through which cinnamoyl sulfonamide hydroxamate derivatives exert their anticancer effects on OSCC.

MATERIALS AND METHODS

The derivatives were synthesized via multi-step processes and then characterized at the molecular level. Flow cytometry assay for DNA content and cell cycle distribution, anisidine/toluidine double staining for apoptosis detection, as well as reverse transcription polymerase chain reaction (RT-PCR) gene expression analysis, were performed on OSCC cell lines exposed to cinnamoyl sulfonamide hydroxamate derivatives.

RESULTS

Flow cytometry unveiled remarkable changes in the distribution of cells throughout the OSCC cell line upon treatment with cinnamoyl sulfonamide hydroxamate derivatives. Consequently, it led to a noticeable decrease in cells at the G0/G1 phase, together with an increase at the S phase, thereby indicating a retardation at various points of the cycle. In addition, apoptotic morphological alterations have been observed by anisidine/toluidine double staining after some treatments with the compounds. RT-PCR analysis showed a marked increase in p21 gene expression levels, further supporting the compounds' ability to induce cell cycle arrest and apoptosis.

CONCLUSION

The research highlighted the potential of cinnamoyl sulfonamide hydroxamate derivatives as candidates for oral cancer, particularly OSCC treatment, shedding light on their operation at the molecular level and paving the way for the development of targeted therapies that could aid in the cure of oral cancer.

摘要

背景

口腔癌是全球主要的公共卫生问题,口腔鳞状细胞癌(OSCC)是其最常见的亚型之一。尽管该疾病在诊断和治疗方面取得了进展,但仍需要开发新的治疗方法以获得更好的治疗效果。

目的

本研究旨在探讨肉桂酰磺酰胺异羟肟酸酯衍生物对OSCC发挥抗癌作用的分子机制。

材料与方法

通过多步合成法合成这些衍生物,然后在分子水平上对其进行表征。对暴露于肉桂酰磺酰胺异羟肟酸酯衍生物的OSCC细胞系进行DNA含量和细胞周期分布的流式细胞术检测、用于凋亡检测的茴香胺/甲苯胺双重染色以及逆转录聚合酶链反应(RT-PCR)基因表达分析。

结果

流式细胞术显示,用肉桂酰磺酰胺异羟肟酸酯衍生物处理后,整个OSCC细胞系中的细胞分布发生了显著变化。因此,导致G0/G1期细胞明显减少,S期细胞增加,从而表明细胞周期在各个阶段均有延迟。此外,在用这些化合物进行一些处理后,通过茴香胺/甲苯胺双重染色观察到了凋亡形态学改变。RT-PCR分析显示p21基因表达水平显著增加,进一步支持了这些化合物诱导细胞周期停滞和凋亡的能力。

结论

该研究突出了肉桂酰磺酰胺异羟肟酸酯衍生物作为口腔癌尤其是OSCC治疗候选药物的潜力,揭示了它们在分子水平上的作用机制,并为开发有助于治愈口腔癌的靶向治疗方法铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/11056768/498d9d75abe2/cureus-0016-00000057236-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/11056768/2a66509caff0/cureus-0016-00000057236-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/11056768/6b9cc8290341/cureus-0016-00000057236-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/11056768/498d9d75abe2/cureus-0016-00000057236-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/11056768/2a66509caff0/cureus-0016-00000057236-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/11056768/6b9cc8290341/cureus-0016-00000057236-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/11056768/498d9d75abe2/cureus-0016-00000057236-i03.jpg

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本文引用的文献

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Targeting p53 pathways: mechanisms, structures, and advances in therapy.靶向 p53 通路:机制、结构和治疗进展。
Signal Transduct Target Ther. 2023 Mar 1;8(1):92. doi: 10.1038/s41392-023-01347-1.
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Basic Methods of Cell Cycle Analysis.细胞周期分析的基本方法。
Int J Mol Sci. 2023 Feb 12;24(4):3674. doi: 10.3390/ijms24043674.
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Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents.天然产物靶向癌症信号通路:探索有前途的抗癌药物。
Biomed Pharmacother. 2022 Jun;150:113054. doi: 10.1016/j.biopha.2022.113054. Epub 2022 Apr 30.
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Cinnamic acid hybrids as anticancer agents: A mini-review.肉桂酸杂合物作为抗癌剂:小型综述。
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The global challenge of cancer.癌症的全球挑战。
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Oral cancer diagnosis and perspectives in India.印度口腔癌的诊断与展望
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