Department of Biochemistry, Basic Medical College of Jilin Medical University, Jilin, People's Republic of China.
Faculty of Medicine, Beihua University, Jilin, People's Republic of China.
Phytother Res. 2024 Oct;38(10):4967-4981. doi: 10.1002/ptr.7868. Epub 2023 May 8.
Most human papillomavirus (HPV) types, including HPV16 and HPV18, are closely related to the occurrence of cervical cancer, predominantly through the action of viral oncoproteins E6 and E7. Curcumin, the active ingredient of the turmeric plant, has been gaining attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In the present study, the HPV-positive cervical cancer cells HeLa and CaSki were treated with curcumin, and the results showed that curcumin has a dose-dependent and time-dependent inhibitory effect on cell viability. In addition, apoptosis induction was further quantitatively confirmed through flow cytometric analysis. Furthermore, the influence of different concentrations of curcumin on the mitochondrial membrane potential was evaluated through JC-1 staining and found to dramatically decrease the membrane potential in treated HeLa and CaSki cells, suggesting the critical role of the mitochondrial pathway in their apoptosis-inducing effect. This study also demonstrated the wound-healing potential of curcumin, and the results of transwell assays showed that curcumin treatment inhibited HeLa and CaSki cell invasion and migration in a dose-dependent manner compared with the control treatment. Curcumin also downregulated the expression of Bcl-2, N-cadherin, and Vimentin and upregulated the expression of Bax, C-caspase-3, and E-cadherin in both cell lines. Further research showed that curcumin also selectively inhibited the expression of the viral oncoproteins E6 and E7, as demonstrated by western blot analysis; moreover, the downregulation of E6 was more significant than that of E7. Our research also showed that coculture with cells infected with siE6 lentivirus (siE6 cells) can inhibit the proliferation, invasion, and metastasis of HPV-positive cells. While the siE6 cells were also treated with curcumin, the effect of curcumin monotherapy was offset. In summary, our research shows that curcumin regulates the apoptosis, migration, and invasion of cervical cancer cells, and the mechanism may be related to its ability to downregulate E6. This study provides a foundation for future research on the prevention and treatment of cervical cancer.
大多数人乳头瘤病毒（HPV）类型，包括 HPV16 和 HPV18，与宫颈癌的发生密切相关，主要通过病毒癌蛋白 E6 和 E7 的作用。姜黄素是姜黄植物的活性成分，在过去的二十年中，作为一种抗氧化剂、抗炎剂和抗癌剂受到了关注。在本研究中，用姜黄素处理 HPV 阳性宫颈癌细胞 HeLa 和 CaSki，结果表明姜黄素对细胞活力具有剂量依赖性和时间依赖性的抑制作用。此外，通过流式细胞术分析进一步定量证实了细胞凋亡的诱导。此外，通过 JC-1 染色评估不同浓度姜黄素对线粒体膜电位的影响，发现处理的 HeLa 和 CaSki 细胞中膜电位显著降低，提示线粒体途径在其诱导凋亡作用中起关键作用。这项研究还证明了姜黄素的伤口愈合潜力，Transwell 测定的结果表明，与对照处理相比，姜黄素处理以剂量依赖的方式抑制了 HeLa 和 CaSki 细胞的侵袭和迁移。姜黄素还下调了这两种细胞系中 Bcl-2、N-钙粘蛋白和波形蛋白的表达，上调了 Bax、C-半胱天冬酶-3 和 E-钙粘蛋白的表达。进一步的研究表明，姜黄素还通过 Western blot 分析选择性抑制了病毒癌蛋白 E6 和 E7 的表达；此外，E6 的下调比 E7 更显著。我们的研究还表明，与感染 siE6 慢病毒的细胞（siE6 细胞）共培养可以抑制 HPV 阳性细胞的增殖、侵袭和转移。当 siE6 细胞也用姜黄素处理时，姜黄素单药治疗的效果被抵消。总之，我们的研究表明，姜黄素调节宫颈癌细胞的凋亡、迁移和侵袭，其机制可能与其下调 E6 的能力有关。这项研究为宫颈癌的预防和治疗提供了依据。
