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.