Chemopreventive Potential of an Ethyl Acetate Fraction from Curcuma Longa is Associated with Upregulation of p57kip2 and Rad9 in the PC-3M Prostate Cancer Cell Line

Background: Turmeric (Curcuma longa) has been shown to possess anti-inflammatory, antioxidant and antitumor properties. However, despite the progress in research with C. longa, there is still a big lacuna in the information on the active principles and their molecular targets. More particularly very little is known about the role of cell cycle genes p57(kip2) and Rad9 during chemoprevention by turmeric and its derivatives especially in prostate cancer cell lines. Methods: Accordingly, in this study, we have examined the antitumor effect of several extracts of C. longa rhizomes by successive fractionation in clonogenic assays using highly metastatic PC-3M prostate cancer cell line. Results: A mixture of isopropyl alcohol: acetone: water: chloroform: and methanol extract of C. longa showed significant bioactivity. Further partition of this extract showed that bioactivity resides in the dichloromethane soluble fraction. Column chromatography of this fraction showed presence of biological activity only in ethyl acetate eluted fraction. HPLC, UV-Vis and Mass spectra studies showed presence three curcuminoids in this fraction besides few unidentified components. Conclusions: From these observations it was concluded that the ethyl acetate fraction showed not only inhibition of colony forming ability of PC-3M cells but also up-regulated cell cycle genes p57(kip2) and Rad9 and further reduced the migration and invasive ability of prostate cancer cells.