Novel Lignan and stilbenoid mixture shows anticarcinogenic efficacy in preclinical PC-3M-luc2 prostate cancer model

• Published in: PloS one Vol. 9; no. 4; p. e93764
• Main Authors: Yatkin, Emrah, Polari, Lauri, Laajala, Teemu D, Smeds, Annika, Eckerman, Christer, Holmbom, Bjarne, Saarinen, Niina M, Aittokallio, Tero, Mäkelä, Sari I
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Acids; Androgens; Animal models; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Bioavailability; Biology and Life Sciences; Body weight; Cancer; Cancer therapies; Care and treatment; Cell cycle; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Chemistry; Diagnosis; Dosage and administration; Effectiveness; Epidemiology; Food; Functional foods & nutraceuticals; Furans - pharmacology; Furans - therapeutic use; Genetic aspects; Health aspects; Health risks; Heterografts; Humans; Knots; Laboratories; Ligands; Lignans; Lignans - pharmacology; Lignans - therapeutic use; Male; Matairesinol; Medicine and Health Sciences; Mice; Mouse devices; Multivariate analysis; Nutrient deficiency; Phenolic compounds; Phenols; Physical Sciences; Pine; Pine trees; Pinosylvin; Pinus sylvestris; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plants; Product development; Prostate cancer; Prostatic Neoplasms - drug therapy; Research and Analysis Methods; Resveratrol; Stilbenes - pharmacology; Stilbenes - therapeutic use; Studies; TNF-Related Apoptosis-Inducing Ligand - pharmacology; TRAIL protein; Tumor necrosis factor-TNF; Vascularization; Wood; Xenografts; Finland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0093764

Prostate cancer is the most common cancer of men in the Western world, and novel approaches for prostate cancer risk reduction are needed. Plant-derived phenolic compounds attenuate prostate cancer growth in preclinical models by several mechanisms, which is in line with epidemiological findings suggesting that consumption of plant-based diets is associated with low risk of prostate cancer. The objective of this study was to assess the effects of a novel lignan-stilbenoid mixture in PC-3M-luc2 human prostate cancer cells in vitro and in orthotopic xenografts. Lignan and stilbenoid -rich extract was obtained from Scots pine (Pinus sylvestris) knots. Pine knot extract as well as stilbenoids (methyl pinosylvin and pinosylvin), and lignans (matairesinol and nortrachelogenin) present in pine knot extract showed antiproliferative and proapoptotic efficacy at ≥ 40 μM concentration in vitro. Furthermore, pine knot extract derived stilbenoids enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced apoptosis already at ≥ 10 μM concentrations. In orthotopic PC-3M-luc2 xenograft bearing immunocompromized mice, three-week peroral exposure to pine knot extract (52 mg of lignans and stilbenoids per kg of body weight) was well tolerated and showed anti-tumorigenic efficacy, demonstrated by multivariate analysis combining essential markers of tumor growth (i.e. tumor volume, vascularization, and cell proliferation). Methyl pinosylvin, pinosylvin, matairesinol, nortrachelogenin, as well as resveratrol, a metabolite of pinosylvin, were detected in serum at total concentration of 7-73 μM, confirming the bioavailability of pine knot extract derived lignans and stilbenoids. In summary, our data indicates that pine knot extract is a novel and cost-effective source of resveratrol, methyl pinosylvin and other bioactive lignans and stilbenoids. Pine knot extract shows anticarcinogenic efficacy in preclinical prostate cancer model, and our in vitro data suggests that compounds derived from the extract may have potential as novel chemosensitizers to TRAIL. These findings promote further research on health-related applications of wood biochemicals.