Embelin is an active ingredient of traditional herbal medicine that exhibits anti-
tumor effects in human
prostate cancer cells. However,
therapeutic effect of
embelin in combination with conventional
radiation therapy is not yet determined. In this study, we evaluate the sensitizing potential of
embelin on ionizing radiation (IR) in a human
prostate cancer model. In vitro,
embelin combined with radiation potently suppressed
prostate cancer PC-3 cell proliferation that was associated with S and G2/M arrest in cell cycle. Moreover, the combination treatment promoted
caspase-independent apoptosis, as evidenced by the increased apoptotic cell death without
caspase-3 activation, but not autophagy. Clonogenic survival assay showed that S-phase arrest was required for
embelin-mediated radiosensitization. In vivo,
embelin significantly improved
tumor response to X-ray radiation in the PC-3 xenograft model. Combination
therapy produced enhanced
tumor growth delay and prolonged time to progression, with minimal systemic toxicity. Immunohistochemistry studies showed that
embelin plus IR significantly inhibited cell proliferation, induced apoptosis, and decreased microvessel density in
tumors as compared with either treatment alone, suggesting an enhanced combinatory inhibition on
tumor suppression and angiogenesis. Our results demonstrate that
embelin significantly facilitates
tumor suppression by
radiation therapy both in vitro and in vivo in the
prostate cancer model. This finding warrants
embelin as a novel adjuvant therapeutic candidate for the treatment of
hormone-refractory
prostate cancer that is resistant to
radiation therapy.