Abstract
Cancer causes considerable morbidity and mortality across the world. Socioeconomic, environmental, and lifestyle factors contribute to the increasing cancer prevalence, bespeaking a need for effective prevention and treatment strategies. Phytochemicals like plant polyphenols are generally considered to have anticancer, anti-inflammatory, antiviral, antimicrobial, and immunomodulatory effects, which explain their promotion for human health. The past several decades have contributed to a growing evidence base in the literature that demonstrate ability of polyphenols to modulate multiple targets of carcinogenesis linking models of cancer characteristics (i.e., hallmarks and nutraceutical-based targeting of cancer) via direct or indirect interaction or modulation of cellular and molecular targets. This evidence is particularly relevant for the lignans, an ubiquitous, important class of dietary polyphenols present in high levels in food sources such as flaxseed. Literature evidence on lignans suggests potential benefit in cancer prevention and treatment. This review summarizes the relevant chemical and pharmacokinetic properties of dietary polyphenols and specifically focuses on the biological targets of flaxseed lignans. The consolidation of the considerable body of data on the diverse targets of the lignans will aid continued research into their potential for use in combination with other cancer chemotherapies, utilizing flaxseed lignan-enriched natural products.
Link to Full Text
Key Points
Cancer remains a significant unmet medical need despite the extensive research into possible pharmaceutical solutions to tackle the various cancer phenotypes. To address this global health dilemma, a “broad-spectrum therapeutic approach” for cancer mitigation may be required.
This review with 662 references assesses both human and preclinical studies which have suggested synergism of polyphenols such as flaxseed lignans with existing therapeutics and, therefore, represent possible candidates for chemoprevention or as combination treatments with standard therapies such as chemotherapy, radiotherapy, immunotherapy, and gene therapy. Authors Conclusions: The review concludes that dietary polyphenols represent a diverse array of chemical subgroups with evidence of variable efficacy in mitigating cancer risk and progression. Despite epidemiological support of possible benefit, these compounds lack general acceptance as therapeutic modalities in cancer treatment. This likely relates to an incomplete understanding of their mechanisms of action as well as a general lack of understanding of their absorption and pharmacokinetic characteristics resulting too often in exposure levels inadequate to address the disease process. Hence, an important purpose of this article was to review the scientific evidence of the role of flaxseed lignans in chemoprevention and on the growth, survival, and progression of malignant cells. This review consolidates years of unsystematic research with the flaxseed lignans and identifies lignans as having multiple targets and modes of action within the cancer phenotype. These multitargeted effects are broadly grouped as modulation of cell signaling and metabolism, cell growth and differentiation, cell motility and cytoskeletal dynamics, cell cycle, angiogenesis, and apoptosis. Such effects might explain the limited epidemiological evidence of lignan benefit in cancer, but a systematic approach, which includes lignan preclinical studies with translational relevance as well as clinical trials utilizing therapeutically relevant doses, will be needed to clarify their role in cancer. As other pharmaceuticals (e.g., the statin drugs) undergo repurposing to cancer treatment, a systematic investigation of polyphenolics such as the lignans might also harness their potential benefits towards chemoprevention and enhancement of patient longevity and quality of life.