de Assis Carvalho Analine Rosa Barquez, Ferreira Damke Gabrielle Marconi Zago, de Freitas Meirelles Lyvia Eloiza, Pantarotto Souza Raquel, Ratti Bianca Altrao, Damke Edilson, Bruschi Marcos Luciano, Consolaro Marcia Edilaine Lopes, da Silva Vania Ramos Sela
Department of Clinical Analysis and Biomedicine, State University of Maringá, 87020-900, Maringá, Brazil.
Department of Pharmacy, State University of Maringá, 87020-900, Maringá, Brazil.
Anticancer Agents Med Chem. 2025;25(17):1311-1322. doi: 10.2174/0118715206366318250312052617.
In the past few years, the antiproliferative activities of chrysin (5,7-dihydroxyflavone) have garnered significant attention in anticancer drug discovery due to its promising ability to suppress cancer cell proliferation. However, studies on its effects on cervical cancer are limited and have primarily focused on HeLa cells.
In order to better understand its therapeutic potential for cervical cancer, we assessed the antiproliferative and anti-migratory effects of chrysin in a wide range of human-derived cell lines comprising C33A (human papillomavirus/HPV-negative), HeLa (HPV 18-positive), SiHa (HPV 16-positive), and CaSKi (HPV 16 and 18- positive), in comparison to a human epithelial cell line derived from spontaneously immortalized cell, HaCaT.
Cell viability was determined using the MTT assay, while the clonogenic assay evaluated long-term cytotoxicity. Morphological alterations were observed via light microscopy, and cell death was assessed using Annexin V FITC/propidium iodide (PI) staining. Total reactive oxygen species (ROS) levels were measured by fluorescence microscopy, the mitochondrial transmembrane potential was assessed using TMRE, and lipid peroxidation was analyzed using DPPP. Additionally, wound healing migration and cell invasion assays were conducted.
Chrysin selectively inhibited cell proliferation and induced apoptosis in every cervical cancer cell line assessed while exerting minimal effects on HaCaT cells. Additionally, it triggered mitochondrial redox imbalance and significantly suppressed both migration and invasion of cervical cancer cells.
Based on these results, chrysin appears to be a promising candidate as an anticancer agent for both HPV-associated and HPV-independent cervical cancers, emphasizing the necessity for further exploration in subsequent studies.
在过去几年中,白杨素(5,7 - 二羟基黄酮)的抗增殖活性因其在抑制癌细胞增殖方面的潜力,在抗癌药物研发中备受关注。然而,关于其对宫颈癌作用的研究有限,且主要集中在HeLa细胞上。
为了更好地了解其对宫颈癌的治疗潜力,我们评估了白杨素对多种人源细胞系的抗增殖和抗迁移作用,这些细胞系包括C33A(人乳头瘤病毒/HPV阴性)、HeLa(HPV 18阳性)、SiHa(HPV 16阳性)和CaSki(HPV 16和18阳性),并与源自自发永生化细胞的人上皮细胞系HaCaT进行比较。
使用MTT法测定细胞活力,克隆形成试验评估长期细胞毒性。通过光学显微镜观察形态学改变,使用膜联蛋白V FITC/碘化丙啶(PI)染色评估细胞死亡。通过荧光显微镜测量总活性氧(ROS)水平,使用四甲基罗丹明乙酯(TMRE)评估线粒体跨膜电位,使用二苯基膦酸(DPPP)分析脂质过氧化。此外,进行了伤口愈合迁移和细胞侵袭试验。
白杨素在评估的每个宫颈癌细胞系中均选择性抑制细胞增殖并诱导凋亡,而对HaCaT细胞的影响最小。此外,它引发线粒体氧化还原失衡,并显著抑制宫颈癌细胞的迁移和侵袭。
基于这些结果,白杨素似乎是一种有前景的抗癌药物候选物,可用于治疗HPV相关和HPV非依赖性宫颈癌,强调了在后续研究中进一步探索的必要性。