Phytosterols and phytostanols and the hallmarks of cancer: a meta-analysis of pre-clinical animal models

Abstract

Background and Purpose Phytosterols and phytostanols are natural products present in vegetable oils, nuts, and seeds, or added to consumer food products and intake is inversely associated with incidence and prognosis of several cancers. Randomised cancer prevention trials in humans are unfeasible due to time and cost yet the cellular processes and signalling cascades that underpin anti-cancer effects of these phytochemicals have been explored extensively in vitro and in preclinical in vivo models. Experimental Approach 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 screen 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. Key Results Phytosterols were most commonly studied and found to reduce primary and metastatic tumour burden in all cancer sites evaluated. Expression of pAKT, and markers of metastasis, angiogenesis, and proliferation were consistently reduced in breast and colorectal cancer. Very high dose treatment (not easily achievable through diet or supplementation in humans) was associated with adverse events including poor gut health and intestinal adenoma development. Conclusion and Implications Phytosterols and phytostanols are already clinically recommended for cardio-vascular 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.

Phytosterol and phytostanol-mediated epigenetic changes in cancer and other non-communicable diseases: a systematic review

“…However, further studies characterising the bioactive compounds and mechanisms of action conferring health benefits are required. PSS enriched in plant-based diets lower pathogenic blood lipids (12,14,58) , are linked to reduced cancer burden and risk (16,17) and a range of other diseases. Our systematic review has collated important knowledge regarding how PSS may act as epigenetic modifiers with the following notable observations.…”

“…Therefore, for the treatment and management of hyperlipidaemia, PSS consumption is recommended by the National Lipid Association, the European Society of Cardiology and the European Atherosclerosis Society (14,15) . In addition, two meta-analyses have concluded that PSS consumption was linked to a reduced risk of developing some cancers in humans (16) and reduced cancer burden in preclinical models (17) . More broadly, PSS have also been proposed to have anti-inflammatory, anti-microbial, blood pressure lowering, anti-diabetic and anti-obesity properties (reviewed in (18) ).…”

“…The exact mechanisms through which PSS exert their effects remain unclear, but previous work has implicated induction of sterol metabolism and transport pathways (30,31) , interference with ligand dependent transcription factor activity (32,33) and inhibition of oncogene signalling (17) . Given the change in steady-state levels of PSS in the body after long-term consumption, a key question is whether PSS, as for various other dietary compounds (34) , may be dietary modifiers of epigenetic gene expression patterns.…”