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没食子酰基 Bergenin 通过降低 Galectin-3 和 MMP-9 的表达抑制人宫颈癌细胞的生长。

Bergenin inhibits growth of human cervical cancer cells by decreasing Galectin-3 and MMP-9 expression.

机构信息

Department of Medical Oncology (Lab.), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.

Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Sci Rep. 2024 Jul 3;14(1):15287. doi: 10.1038/s41598-024-64781-3.

Abstract

Cervical cancer is still the leading cause of cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus. Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent-angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer.

摘要

即使在引入针对人类乳头瘤病毒 (HPV) 的疫苗后,宫颈癌仍然是全球癌症死亡的主要原因,这主要是由于疫苗接种率低,尤其是在发展中国家。宫颈癌主要通过化疗/放疗治疗,具体取决于疾病阶段,并采用顺铂/卡铂为基础的药物治疗方案。这些药物是非特异性的,针对快速分裂的细胞,包括正常细胞,因此需要更安全的选择来降低非靶毒性。与合成药物相比,天然产物提供了一个有吸引力的选择,因为它们具有良好的安全性和靶向癌症多个致癌标志的能力,如炎症、血管生成等。在目前的研究中,我们研究了 Bergenin(4-O-甲基没食子酸的 C-糖苷)的作用,Bergenin 是一种从 Bergenia crassifolia、Caesalpinia digyna 和 Flueggea leucopyrus 等药用植物中分离出来的天然多酚化合物。Bergenin 已被证明具有抗炎、抗溃疡和伤口愈合特性,但最近才意识到其抗癌潜力。我们对用 Bergenin 处理的宫颈癌细胞进行了蛋白质组学分析,发现它影响了癌症的多个标志,包括细胞凋亡、血管生成和肿瘤抑制蛋白。如蛋白质组学分析所示,它还参与了许多与癌症无关的不同细胞过程。进一步的分析表明,Bergenin 通过降低宫颈癌细胞中的关键血管生成蛋白,如半乳糖凝集素 3 和 MMP-9(基质金属蛋白酶 9),是一种有效的血管生成抑制剂。通过分子对接分析进一步了解这种相互作用,表明 MMP-9 与 Galectin-3 相比,对 Bergenin 的亲和力更强。总的来说,我们的数据提供了关于 Bergenin 在宫颈癌细胞中抗血管生成机制的新见解,通过调节半乳糖凝集素 3 和 MMP-9 等多种血管生成蛋白,这使其有必要进一步开发作为宫颈癌的抗癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17b3/11222472/c6d4e6f3e696/41598_2024_64781_Fig1_HTML.jpg

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