Naushad Wasifa, Okeoma Bryson C, Islam Humayun K, Wang Zhen Zhen, Yang Nan, Li XiuMin, Okeoma Chioma M
Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, USA.
Department of Pathology, Westchester Medical Center, Valhalla, NY, Valhalla, USA.
Res Sq. 2024 Nov 21:rs.3.rs-5479739. doi: 10.21203/rs.3.rs-5479739/v1.
We report the effects of berberine (BBR), a benzylisoquinoline alkaloid small molecule on inhibition of HIV infection of cervical cancer cells. We used HeLa cell-derived TZM-bl cell line as a model of cervical cancer and HIV infection. BBR significantly inhibits viral and cancer processes, including expression of cell-associated HIV RNA, secretion of HIV reverse transcriptase, and HIV Tat-mediated LTR promoter transactivation. BBR significantly inhibits HIV-induced cancer cell viability and cell clustering. Besides its ability to inhibit HIV-induced cancer cell viability, BBR inhibits migration and matrix invasion of cervical cancer cells that are infected with HIV or treated with HIV Tat protein. The ability of BBR to inhibit cell clustering, collective cell migration, and cell invasion may have an effect in controlling progression of cervical cancer and HIV since collective migration and invasion are strategies for local tissue infiltration, as well as metastatic invasion in epithelial cancers. Interestingly, molecular docking and dynamic stimulation show that BBR binds HIVIIIB Tat amino acid residues through non- covalent interactions that occurs at multiple sites including LYS71, providing mechanistic insights into BBR regulation HIV infection. The results of the present study suggest that BBR has the potential to inhibit HIV infection and comorbid cervical cancer progression.
我们报告了小檗碱（BBR），一种苄基异喹啉生物碱小分子，对抑制子宫颈癌细胞感染HIV的作用。我们使用源自HeLa细胞的TZM-bl细胞系作为子宫颈癌和HIV感染的模型。BBR显著抑制病毒和癌症相关进程，包括细胞相关HIV RNA的表达、HIV逆转录酶的分泌以及HIV Tat介导的LTR启动子反式激活。BBR显著抑制HIV诱导的癌细胞活力和细胞聚集。除了抑制HIV诱导的癌细胞活力的能力外，BBR还抑制感染HIV或用HIV Tat蛋白处理的子宫颈癌细胞的迁移和基质侵袭。BBR抑制细胞聚集、集体细胞迁移和细胞侵袭的能力可能对控制子宫颈癌和HIV的进展有作用，因为集体迁移和侵袭是局部组织浸润以及上皮癌转移侵袭的策略。有趣的是，分子对接和动力学模拟表明，BBR通过包括LYS71在内的多个位点发生的非共价相互作用与HIVIIIB Tat氨基酸残基结合，为BBR调节HIV感染提供了机制性见解。本研究结果表明，BBR有潜力抑制HIV感染和合并的子宫颈癌进展。
