College of Public Health, The Ohio State University, Columbus, OH, USA.
Gynecol Oncol. 2011 Nov;123(2):401-6. doi: 10.1016/j.ygyno.2011.07.023. Epub 2011 Aug 9.
Cervical cancer is the second most common female cancer worldwide, and it remains a challenge to manage preinvasive and invasive lesions. Food-based cancer prevention entities, such as black raspberries and their derivatives, have demonstrated a marked ability to inhibit preclinical models of epithelial cancer cell growth and tumor formation. Here, we extend the role of black raspberry-mediated chemoprevention to that of cervical carcinogenesis.
Three human cervical cancer cell lines, HeLa (HPV16-/HPV18+, adenocarcinoma), SiHa (HPV16+/HPV18-, squamous cell carcinoma) and C-33A (HPV16-/HPV18-, squamous cell carcinoma), were treated with a lyophilized black raspberry ethanol extract (RO-ET) at 25, 50, 100 or 200μg/ml for 1, 3 and 5days, respectively. Cell proliferation was measured by WST1 (tetrazolium salt cleavage) assays. Flow cytometry (propidium iodide and Annexin V staining) and fluorescence microscopy analysis were used to measure apoptotic cell changes.
We found that non-toxic levels of RO-ET significantly inhibited the growth of human cervical cancer cells, in a dose-dependent and time-dependent manner to a maximum of 54%, 52% and 67%, respectively (p<0.05). Furthermore, cell growth inhibition was persistent following short-term withdrawal of RO-ET from the culture medium. Flow cytometry and fluorescence microscopy demonstrated RO-ET-induced apoptosis in all cell lines.
Black raspberries and their bioactive components represent promising candidates for future phytochemical-based mechanistic pathway-targeted cancer prevention strategies.
宫颈癌是全球第二大常见的女性癌症,对其癌前病变和侵袭性病变的处理仍然是一个挑战。以食物为基础的癌症预防实体,如黑覆盆子及其衍生物,已显示出显著抑制上皮癌细胞生长和肿瘤形成的临床前模型的能力。在这里,我们将黑覆盆子介导的化学预防作用扩展到宫颈癌的发生。
用冻干黑覆盆子乙醇提取物(RO-ET)处理三种人宫颈癌细胞系(HeLa[HPV16-/HPV18+,腺癌]、SiHa[HPV16+/HPV18-,鳞状细胞癌]和 C-33A[HPV16-/HPV18-,鳞状细胞癌]),浓度分别为 25、50、100 或 200μg/ml,分别处理 1、3 和 5 天。通过 WST1(四唑盐裂解)测定法测量细胞增殖。流式细胞术(碘化丙啶和 Annexin V 染色)和荧光显微镜分析用于测量凋亡细胞变化。
我们发现,非毒性水平的 RO-ET 显著抑制了人宫颈癌细胞的生长,呈剂量依赖性和时间依赖性,最大抑制率分别为 54%、52%和 67%(p<0.05)。此外,RO-ET 从培养基中短暂撤出后,细胞生长抑制仍然持续。流式细胞术和荧光显微镜显示 RO-ET 诱导了所有细胞系的细胞凋亡。
黑覆盆子及其生物活性成分代表了未来基于植物化学的机制途径靶向癌症预防策略的有前途的候选物。