Pathways Affected by Falcarinol-Type Polyacetylenes and Implications for Their Anti-Inflammatory Function and Potential in Cancer Chemoprevention

Abstract

Polyacetylene phytochemicals are emerging as potentially responsible for the chemoprotective effects of consuming apiaceous vegetables. There is some evidence suggesting that polyacetylenes (PAs) impact carcinogenesis by influencing a wide variety of signalling pathways, which are important in regulating inflammation, apoptosis, cell cycle regulation, etc. Studies have shown a correlation between human dietary intake of PA-rich vegetables with a reduced risk of inflammation and cancer. PA supplementation can influence cell growth, gene expression and immunological responses, and has been shown to reduce the tumour number in rat and mouse models. Cancer chemoprevention by dietary PAs involves several mechanisms, including effects on inflammatory cytokines, the NF-κB pathway, antioxidant response elements, unfolded protein response (UPR) pathway, growth factor signalling, cell cycle progression and apoptosis. This review summarises the published research on falcarinol-type PA compounds and their mechanisms of action regarding cancer chemoprevention and also identifies some gaps in our current understanding of the health benefits of these PAs.

Carrot Intake is Consistently Negatively Associated with Cancer Incidence: A Systematic Review and Meta-Analysis of Prospective Observational Studies

“…The relatively uniform effect across different cancer types indicates a mechanism of action that is not confined to a particular organ, such as modulation of inflammation (Alfurayhi, Huang, and Brandt 2023). The inter-study heterogeneity in the meta-analysis was moderate in the data on carrot/α-carotene intakes (Figure 2) and low in the data on plasma α-carotene (Figure 4), respectively.…”

“…We therefore hypothesize that carrots are unique among most vegetables and fruits due to their content of one or more specific non-nutrient bioactive secondary metabolites, where carrot is the major dietary source. This applies to specific polyacetylenes and isocoumarins, each of which have been implicated as potential anti-cancer constituents based on in vitro studies or animal trials (Snene et al 2017;Kobaek-Larsen et al 2019;Alfurayhi, Huang, and Brandt 2023). Carrots provide approximately 85% (range 82-94%) of dietary α-carotene across different food cultures, providing even stronger correlations with carrot intake than β-carotene (O'Neill et al 2001;Hendrickson et al 2013;Lee et al 2013).…”

Antioxidant and Anti-Inflammatory Mechanisms of Lipophilic Fractions from Polyscias fruticosa Leaves Based on Network Pharmacology, In Silico, and In Vitro Approaches

“…Dihydroactinidiolide showed a strong affinity with NR1l2 (−7.5 kcal/mol), while (Z)-1,3-phytadiene and falcarinol had robust conformations with PTGS2 (−7.1 and −7.1 kcal/mol). Falcarinol, a polyacetylenic oxylipin, offers several biological functions, such as anti-inflammatory, anti-diabetic, cytotoxic, chemopreventive, and anti-neoplastic effects [58,59]. In vitro and in vivo studies have documented the anti-inflammatory ability of falcarinol via the downregulation of NF-κB activity and the expression of inflammatory factors [58,59].…”

“…Falcarinol, a polyacetylenic oxylipin, offers several biological functions, such as anti-inflammatory, anti-diabetic, cytotoxic, chemopreventive, and anti-neoplastic effects [58,59]. In vitro and in vivo studies have documented the anti-inflammatory ability of falcarinol via the downregulation of NF-κB activity and the expression of inflammatory factors [58,59]. Stigmasterol and (3β,5α)-stigmasta-7,16-dien-3-ol exhibited strong binding activities and stable conformations with KEAP1 (−9.9 and −9.4 kcal/mol, respectively) and PTGS2 (−8.9 and −8.8 kcal/mol, respectively).…”

Dietary carrot intake compared favourably with three other vegetable groups in protection against incidence of cancers: A systematic review and meta-analysis

“…

High consumption of fruits and vegetables has been associated with reduced risk of cancers and other degenerative diseases, although the overall association is weak for breast, colorectal, lung, and prostate cancer (1)(2) , suggesting that protective effects may be peculiar to specific fruits or vegetables. The present meta-analysis explored the assertion that carrots may contribute a unique protective effect compared with other common vegetables, possibly owing to their content of highly bioactive polyacetylenes (3) . We hypothesized that (1) carrot consumption is associated with reduced risks of cancers, and (2) carrots offer greater or equal protective effects compared with tomatoes, cruciferous, and green leafy vegetables.

…”