Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo

Abstract

BACKGROUND. Earlier work from our laboratory highlighted the therapeutic potential of curcumin (turmeric), used as a dietary ingredient and as a natural anti-in¯ammatory agent in India and other Southeast Asian countries. This agent was shown to decrease the proliferative potential and induce the apoptosis potential of both androgen-dependent and androgenindependent prostate cancer cells in vitro, largely by modulating the apoptosis suppressor proteins and by interfering with the growth factor receptor signaling pathways as exempli®ed by the EGF-receptor. To extend these observations made in vitro and to study the ef®cacy of this potential anti-cancer agent in vivo, the growth of LNCaP cells as heterotopically implanted tumors in nude mice was followed. METHODS. The androgen-dependent LNCaP prostate cancer cells were grown, mixed with Matrigel and injected subcutaneously into nude mice. Experimental group received a synthetic diet containing 2% curcumin for up to 6 weeks. At the end point, sections taken from the excised tumors were evaluated for pathology, cell proliferation, apoptosis, and vascularity. RESULTS. Curcumin causes a marked decrease in the extent of cell proliferation as measured by the BrdU incorporation assay and a signi®cant increase in the extent of apoptosis as measured by an in situ cell death assay. Moreover, a signi®cant decrease in the microvessel density as measured by the CD31 antigen staining was also seen. CONCLUSIONS. Curcumin could be a potentially therapeutic anti-cancer agent, as it signi®cantly inhibits prostate cancer growth, as exempli®ed by LNCaP in vivo, and has the potential to prevent the progression of this cancer to its hormone refractory state. Prostate 47:293±303,

Therapeutic Efficacy of Curcumin/TRAIL Combination Regimen for Hormone-Refractory Prostate Cancer

“…cell lines (22)(23)(24)(25)(26)(27). In animal studies, curcumin was shown to induce regression of prostate cancer xenografts Mice in nude mice (28). There is also some evidence suggesting that curcumin is antiangiogenic (29,30) and may en-Male Balb/c nude mice between 6 and 8 weeks of age were obtained from the National Cancer Institute hance the anticancer activity of chemotherapy or reduce its toxicity (31,32).…”

Androgen responsive and refractory prostate cancer cells exhibit distinct curcumin regulated transcriptome

“…5 The biological effect of curcumin and its recently identified targets like NFκB, beta-catenin have been reviewed in detail. 6,7 Laboratory studies have shown the effectiveness of curcumin in prostate cancer chemoprevention both by using in vitro and in vivo models. [8][9][10] Recently synergism in the inhibition of growth of PC3 prostate tumor xenografts in nude mice was demonstrated with curcumin in combination with phenethyl isothiocyanate.…”

Inducible Nitric Oxide Synthase-Vascular Endothelial Growth Factor Axis: A Potential Target to Inhibit Tumor Angiogenesis by Dietary Agents

“…Inhibits endothelial cell proliferation and migration [123] Inhibits tumor microvessels in prostate tumor xenograft [20] Decreases VEGF expression [110,124] Curcumin Turmeric Decreases iNOS and VEGF expression [61,95,110] Inhibits microvessels density in LNCaP prostate and HepG2 liver tumor xenografts [95,137] Indole-3-carbinol Cruciferous vegetables…”