Food Science & Nutrition, University of Leeds, Leeds, West Yorkshire, UK.
Crit Rev Food Sci Nutr. 2022;62(5):1145-1165. doi: 10.1080/10408398.2020.1835820. Epub 2020 Nov 25.
Phytosterols and phytostanols are natural products present in vegetable oils, nuts, and seeds, or added to consumer food products whose intake is inversely associated with incidence and prognosis of several cancers. Randomized cancer prevention trials in humans are unfeasible due to time and cost yet the cellular processes and signaling cascades that underpin anti-cancer effects of these phytochemicals have been explored extensively in vitro and in preclinical in vivo models. Here we have performed an original systematic review, meta-analysis, and qualitative interpretation of literature published up to June 2020. MEDLINE, Scopus, and hand-searching identified 408 unique records that were screened leading to 32 original articles that had investigated the effects of phytosterols or phytostanols on cancer biology in preclinical models. Data was extracted from 22 publications for meta-analysis. Phytosterols were most commonly studied and found to reduce primary and metastatic tumor burden in all cancer sites evaluated. Expression of pAKT, and markers of metastasis (alkaline phosphatase, matrix metalloproteases, epithelial to mesenchymal transcription factors, lung and brain colonization), angiogenesis (vascular endothelial growth factor, CD31), and proliferation (Ki67, proliferating cell nuclear antigen) were consistently reduced by phytosterol treatment in breast and colorectal cancer. Very high dose treatment (equivalent to 0.2-1 g/kg body weight not easily achievable through diet or supplementation in humans) was associated with adverse events including poor gut health and intestinal adenoma development. Phytosterols and phytostanols are already clinically recommended for cardiovascular disease risk reduction, and represent promising anti-cancer agents that could be delivered in clinic and to the general population at low cost, with a well understood safety profile, and now with a robust understanding of mechanism-of-action.
植物甾醇和植物甾烷醇是存在于植物油、坚果和种子中的天然产物，或者被添加到消费者食品中，其摄入量与几种癌症的发病率和预后呈负相关。由于时间和成本的原因，在人体中进行随机癌症预防试验是不可行的，但这些植物化学物质的抗癌作用的细胞过程和信号级联已经在体外和临床前体内模型中得到了广泛的研究。在这里，我们对截至 2020 年 6 月发表的文献进行了原始的系统评价、荟萃分析和定性解释。通过 MEDLINE、Scopus 和手工检索，共确定了 408 个独特的记录，经过筛选，得出了 32 篇原始文章，这些文章研究了植物甾醇或植物甾烷醇对临床前模型中癌症生物学的影响。从 22 篇出版物中提取数据进行荟萃分析。植物甾醇是最常被研究的，并且在所有评估的癌症部位都发现可以减少原发性和转移性肿瘤负担。在乳腺癌和结直肠癌中，植物甾醇处理后，pAKT 的表达以及转移标志物（碱性磷酸酶、基质金属蛋白酶、上皮到间充质转录因子、肺和脑定植）、血管生成（血管内皮生长因子、CD31）和增殖（Ki67、增殖细胞核抗原）标志物均降低。非常高剂量的治疗（相当于 0.2-1 g/kg 体重，通过饮食或补充剂在人体内不易达到）与不良事件有关，包括肠道健康状况不佳和肠道腺瘤发展。植物甾醇和植物甾烷醇已经被临床推荐用于降低心血管疾病风险，它们是有前途的抗癌药物，可以以低成本在临床上和一般人群中使用，具有良好的安全性，并且现在对作用机制有了更深入的了解。
