**6. Conclusions**

Food plants of the Apiaceae and Araliaceae families rich in PAs have important potential regarding cancer prevention. The findings reviewed here (Table 1) consistently support that PAs are anti-neoplastic natural phytochemicals with the potential for advancement into multiple applications in cancer prevention and treatment and as leading compounds in the discovery of new anticancer drugs. The mechanisms of the action attributed to PAs are similar to those of many other anticancer drugs, which include triggering cell cycle arrest, apoptosis, UPR and reducing inflammation but potentially with lower toxic side effects. The PA concentrations in widely consumed vegetables such as carrots are sufficiently high to potentially provide substantial chemo-preventive effects within the recommended vegetable and fruit intake of 400 g per day while at the same time being sufficiently low to exclude concerns about toxicity from these dietary sources. PAs have significant inhibitory effects on multiple cancer cell pathways, indicating anti-proliferative and anti-tumorigenic properties.

Nevertheless, much work still needs to be carried out to assess and possibly develop the medical development of PAs. Despite being widely distributed in plants, PAs are instable and present in relatively small amounts, which makes it challenging to isolate abundant polyacetylenes from natural sources for large-scale experiments. Improved isolation methods or the development of improved stereospecific chemical synthesis procedures will provide better feasibility for further study. Future studies are needed to determine the safe doses of PAs in humans, which is a prerequisite for any non-food application, whether as food supplements or drugs. In this regard, additional studies are needed on animals and humans for a better determination of the toxicological effects of PAs. Pharmacokinetic studies on PAs are limited, and the pharmacological actions of many PAs are unknown. Advancing this research will provide a scientific foundation for assessments of

their potential for clinical applications and new drug development. NF-κB pathways are influenced by PAs, indicating their significance in terms of not only cancer prevention and treatment but also various other biological processes. However, future studies should focus on investigating the exact mechanism of action of PAs, particularly on NF-κB pathways, to distinguish the influence of PAs on gene transcription, translation or post-translation functions, such as enzymatic activity. Animal experiments, clinical studies and human intervention studies must be conducted to investigate and compare health benefits of PAs in whole foods or isolated PA metabolites using biomarkers indicating inflammation and other cancer-related processes to guide the optimisation of the implementation of affordable food-based cancer prevention programmes.


**Table 1.** Studies of polyacetylene compounds extracted from or contained in natural food and herbs and their applications, doses, time and effect or pathway assessed.

**Author Contributions:** Investigation, figure design, writing—original draft preparation, writing—review and editing, R.A.; supervision, writing—review and editing, L.H.; supervision, writing—review and editing, K.B. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was funded by Qassim University, Qassim, KSA. The funder had no role in data collection, data interpretation, or writing of the review.

**Data Availability Statement:** Data are contained within the article.

**Acknowledgments:** We thank M. Kobæk-Larsen for dose data supplementary to [114].

**Conflicts of Interest:** R.A. and K.B. declare no conflict of interest. L.H. is a consultant and scientific advisor for Bioperfectus Technologies, and a director of Bioperfectus U.K. Limited.
