Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Drug Dev Ind Pharm. 2023 Oct;49(10):658-665. doi: 10.1080/03639045.2023.2268739. Epub 2023 Nov 9.
Kaempferol, the natural bioactive flavonoid, has been utilized as an efficient anti-breast cancer compound. In the current study, the Kaempferol's cellular uptake and its aqueous solubility were improved by using human serum albumin (HSA) as the Kaempferol adjuvant and encapsulating it with the folate-linked chitosan polymer to evaluate the apoptotic, activity of the novel-formulated Kaempferol in human MCF-7 breast cancer cells.
The folate-linked chitosan-coated Kaempferol/HSA nano-transporters (FCKH-NTs) were synthesized and characterized using FTIR, FESEM, DLS, and Zeta potential analysis. The nano-transporters' selective cytotoxicity was studied by applying an MTT assay on the cancerous MCF-7 cells compared with normal HFF cell lines. Cell death type determination was determined by analyzing the expression of apoptotic (BAX and Cas-8) and anti-apoptotic genes (BCL2 and NF-κB). The FCKH-NTs apoptotic activity was verified by studying the flow cytometry and AO/PI staining results.
The 126-nm FCKH-NTs (PDI = 0.282) selectively induced apoptotic death in human MCF-7 breast cancer cells by up-regulating the BAX, Nf- κB, and Cas-8 gene expression. The apoptotic activity of FCKH-NTs was verified by detecting the SubG1-arrested cancer cells and increased apoptotic bodies in AO/PI staining images.
The FCKH-NTs exhibited a selective-cytotoxic impact on human MCF-7 breast cancer cells compared with normal HFF cells, which can be due to the folate receptor-mediated endocytosis mechanism of the nano-transporters. Therefore, the FCKH-NTs have the potential to be used as a selective anti-breast cancer compound.
山奈酚是一种天然生物活性黄酮类化合物,已被用作有效的抗乳腺癌化合物。在本研究中,通过使用人血清白蛋白 (HSA) 作为山奈酚佐剂并将其用叶酸连接的壳聚糖聚合物包封来改善山奈酚的细胞摄取和其水溶解度,以评估新型山奈酚在人 MCF-7 乳腺癌细胞中的凋亡活性。
合成并使用傅里叶变换红外光谱 (FTIR)、FESEM、DLS 和 Zeta 电位分析对叶酸连接的壳聚糖包覆的山奈酚/HSA 纳米转运体 (FCKH-NTs) 进行了表征。通过将 MTT 测定法应用于癌细胞 MCF-7 与正常 HFF 细胞系比较,研究了纳米转运体的选择性细胞毒性。通过分析凋亡 (BAX 和 Cas-8) 和抗凋亡基因 (BCL2 和 NF-κB) 的表达来确定细胞死亡类型。通过研究流式细胞术和 AO/PI 染色结果验证了 FCKH-NTs 的凋亡活性。
粒径为 126nm 的 FCKH-NTs(PDI=0.282)通过上调 BAX、Nf-κB 和 Cas-8 基因的表达,选择性诱导人 MCF-7 乳腺癌细胞发生凋亡性死亡。通过检测 SubG1 期停滞的癌细胞和 AO/PI 染色图像中增加的凋亡小体,验证了 FCKH-NTs 的凋亡活性。
与正常 HFF 细胞相比,FCKH-NTs 对人 MCF-7 乳腺癌细胞表现出选择性细胞毒性,这可能是由于纳米转运体的叶酸受体介导的内吞作用机制。因此,FCKH-NTs 有可能用作选择性抗乳腺癌化合物。