Bergenin 通过降低 Galectin-3 和 MMP-9 的表达来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.
发表日期:2024 Jul 03
作者:
Ravi Chauhan, Lakshay Malhotra, Ashna Gupta, Gunjan Dagar, Mohini Mendiratta, Tariq Masoodi, Sheema Hashem, Sara Al Marzooqi, Dayasagar Das, Shahab Uddin, Abdul Samath Ethayathulla, Muzafar A Macha, Ammira Al-Shabeeb Akil, Ranjit Kumar Sahoo, Ekta Rai, Ajaz A Bhat, Mayank Singh
来源:
DIABETES & METABOLISM
摘要:
即使在引入人乳头瘤病毒 (HPV) 疫苗后,由于疫苗覆盖率较低,尤其是在发展中国家,宫颈癌仍然是全球癌症死亡的主要原因。宫颈癌主要通过化疗/放疗进行治疗,具体取决于疾病阶段,采用卡铂/顺铂为基础的药物方案。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脱靶毒性。与合成药物相比,天然产品提供了一种有吸引力的选择,因为它们具有完善的安全性,并且能够针对癌症的多种致癌标志,如炎症、血管生成等。在当前的研究中,我们研究了岩白菜素(Bergenin)(C-糖苷)的作用。 4-O-甲基没食子酸),一种天然多酚化合物,从药用植物中分离出来,如白白菜、Caesalpinia digyna 和 Flueggea leucopyrus。岩白菜素已被证明具有抗炎、抗溃疡和伤口愈合特性,但其抗癌潜力直到最近才被认识到。我们对用岩白菜素处理的宫颈癌细胞进行了蛋白质组学分析,发现它可以影响癌症的多种特征,包括细胞凋亡、血管生成和肿瘤抑制蛋白。正如我们的蛋白质组分析所示,它还参与许多与癌症无关的不同细胞过程。进一步的分析表明,岩白菜素通过减少宫颈癌细胞中半乳糖凝集素 3 和 MMP-9(基质金属蛋白酶 9)等关键血管生成蛋白,成为一种有效的血管生成剂。使用分子对接分析进一步了解了这种相互作用,表明与 Galectin-3 相比,MMP-9 对岩白菜素具有更高的亲和力。总而言之,我们的数据通过调节 Galectin-3 和 MMP-9 等多种血管生成蛋白,为宫颈癌细胞中岩白菜素的抗血管生成机制提供了新的见解,这保证了其作为宫颈癌抗癌剂的进一步开发。© 2024。作者。
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.© 2024. The Author(s).