Several epigenetic alterations leading to constitutively active mitogenic and cell-survival signaling, and loss of apoptotic response are causally involved in self-sufficiency of
prostate cancer (PCA) cells toward uncontrolled growth, and increased secretion of pro-angiogenic factors. Therefore, one targeted approach for PCA prevention, growth control and/or treatment could be inhibition of epigenetic molecular events involved in PCA growth, progression and angiogenesis. In this regard,
silibinin/
silymarin (
silibinin is the major active compound in
silymarin) has shown promising efficacy. Our extensive studies with
silibinin/
silymarin and PCA cells have shown the pleiotropic anticancer effects leading to cell growth inhibition in culture and nude mice. The underlying mechanisms of
silibinin/
silymarin efficacy against PCA involve alteration in cell cycle progression, and inhibition of mitogenic and cell survival signaling, such as
epidermal growth factor receptor,
insulin-like growth factor receptor type I and
nuclear factor kappa B signaling.
Silibinin also synergizes the
therapeutic effects of
doxorubicin in PCA cells, making it a strong candidate for
combination chemotherapy.
Silibinin/
silymarin also inhibits the secretion of proangiogenic factors from
tumor cells, and causes growth inhibition and apoptotic death of endothelial cells accompanied by disruption of capillary tube formation on
Matrigel. More importantly,
silibinin inhibits the growth of in vivo advanced human prostate
tumor xenograft in nude mice. Recently, due to its non-toxic and mechanism-based strong preventive/therapeutic efficacy,
silibinin has entered in phase I clinical trial in
prostate cancer patients.