aDepartment of Genetics and Molecular Biology, Center for Research and Advance Studies, National Polytechnic Institute bUnit of Biomedical Research in Cancer, Institute of Biomedical Research, UNAM/National Cancer Institute cDepartment of Experimental Pathology, National Institute for Medical Sciences and Nutrition Salvador Zubiran, Mexico City, Mexico.
Eur J Cancer Prev. 2013 Nov;22(6):577-84. doi: 10.1097/CEJ.0b013e328360345f.
Cervical neoplasia is one of the most frequent cancers in women and is associated with high-risk human papillomavirus (HPV) infection. Resveratrol, a natural polyphenolic phytochemical, has received considerable interest on the basis of its potential as a chemopreventive agent against human cancer. In this work, we analyzed the type of cell death induced by resveratrol in several cervical cancer cell lines. Resveratrol treatment (150-250 µmol/l) for 48 h increased cell cycle arrest at the G1 phase in C33A (with mutation in p53) and HeLa cells (HPV18 positive), as well as in CaSki and SiHa cell lines (HPV16 positive). Resveratrol treatment induced apoptosis in all cell lines, particularly in CaSki cells, as measured by Annexin-V flow cytometry analysis. There was a decrease in the mitochondrial membrane potential (apoptosis) in HeLa, CaSki, and SiHa cells and an increased lysosomal permeability (autophagy) in C33A, CaLo (HPV18 positive), and HeLa cell lines. Furthermore, when we used the IC50 of each line, we found that resveratrol produces a similar effect, suggesting that this effect is not dependent on the concentration of resveratrol. Interestingly, after resveratrol treatment, the expression of p53 was decreased in HPV18-positive cell lines (CaLo and HeLa) and increased in HPV16-positive cell lines (CaSki and SiHa) and C33A cells. The expression of p65 (an NF-κB subunit) was decreased after treatment in all cell lines except SiHa cells. These data indicate that resveratrol uses different mechanisms to induce cell death in cell lines derived from cervical cancer.
宫颈癌是女性最常见的癌症之一,与高危型人乳头瘤病毒(HPV)感染有关。白藜芦醇是一种天然多酚类植物化学物质,由于其作为人类癌症化学预防剂的潜力而受到广泛关注。在这项工作中,我们分析了白藜芦醇在几种宫颈癌细胞系中诱导的细胞死亡类型。白藜芦醇处理(150-250μmol/L)48 小时可使 C33A(p53 突变)和 HeLa 细胞(HPV18 阳性)以及 CaSki 和 SiHa 细胞系(HPV16 阳性)的细胞周期停滞在 G1 期。白藜芦醇处理诱导所有细胞系,特别是 CaSki 细胞发生凋亡,通过 Annexin-V 流式细胞术分析测量。HeLa、CaSki 和 SiHa 细胞中线粒体膜电位(凋亡)下降,C33A、CaLo(HPV18 阳性)和 HeLa 细胞系中溶酶体通透性(自噬)增加。此外,当我们使用每条线的 IC50 时,我们发现白藜芦醇产生相似的效果,表明该效果不依赖于白藜芦醇的浓度。有趣的是,白藜芦醇处理后,HPV18 阳性细胞系(CaLo 和 HeLa)中 p53 的表达降低,HPV16 阳性细胞系(CaSki 和 SiHa)和 C33A 细胞中 p53 的表达增加。除 SiHa 细胞外,所有细胞系中 p65(NF-κB 亚单位)的表达在治疗后均下降。这些数据表明,白藜芦醇使用不同的机制在源自宫颈癌的细胞系中诱导细胞死亡。