Silymarin consists of a family of
flavonoids (
silybin,
isosilybin,
silychristin,
silydianin and taxifoline) commonly found in the dried fruit of the milk thistle plant Silybum marianum. Although
silymarin's role as an
antioxidant and hepatoprotective agent is well known, its role as an
anticancer agent has begun to emerge. Extensive research within the last decade has shown that
silymarin can suppress the proliferation of a variety of
tumor cells (e.g., prostate, breast, ovary, colon, lung, bladder); this is accomplished through cell cycle arrest at the G1/S-phase, induction of
cyclin-dependent kinase inhibitors (such as p15, p21 and p27), down-regulation of anti-apoptotic gene products (e.g., Bcl-2 and Bcl-xL), inhibition of cell-survival
kinases (AKT, PKC and MAPK) and inhibition of inflammatory
transcription factors (e.g.,
NF-kappaB).
Silymarin can also down-regulate gene products involved in the proliferation of
tumor cells (
cyclin D1, EGFR, COX-2,
TGF-beta, IGF-IR), invasion (MMP-9), angiogenesis (
VEGF) and
metastasis (adhesion molecules). The antiinflammatory effects of
silymarin are mediated through suppression of
NF-kappaB-regulated gene products, including COX-2, LOX, inducible iNOS, TNF and
IL-1. Numerous studies have indicated that
silymarin is a chemopreventive agent in vivo against a variety of
carcinogens/
tumor promoters, including UV light,
7,12-dimethylbenz(a)anthracene (DMBA),
phorbol 12-myristate 13-acetate (PMA) and others.
Silymarin has also been shown to sensitize
tumors to chemotherapeutic agents through down-regulation of the MDR
protein and other mechanisms. It binds to both
estrogen and
androgen receptors, and down-regulates PSA. In addition to its chemopreventive effects,
silymarin exhibits antitumor activity against human
tumors (e.g., prostate and ovary) in rodents. Various clinical trials have indicated that
silymarin is bioavailable and pharmacologically safe. Studies are now in progress to demonstrate the clinical efficacy of
silymarin against various
cancers.