<i>In Vitro</i>Morphological Assessment of Apoptosis Induced by Antiproliferative Constituents from the Rhizomes of<i>Curcuma zedoaria</i>

Abstract

Bioassay-guided isolation of the active hexane fractions of Curcuma zedoaria led to the identification of five pure compounds, namely, curzerenone ( 1 ), neocurdione ( 2 ), curdione ( 3 ), alismol ( 4 ), and zederone ( 5 ) and a mixture of sterols, namely, campesterol ( 6 ), stigmasterol ( 7 ), and β -sitosterol ( 8 ). Alismol has never been reported to be present in Curcuma zedoaria . All isolated compounds except ( 3 ) were evaluated for their cytotoxic activity against MCF-7, Ca Ski, and HCT-116 cancer cell lines and noncancer human fibroblast cell line (MRC-5) using neutral red cytotoxicity assay. Curzerenone and alismol significantly inhibited cell proliferation in human cancer cell lines MCF-7, Ca Ski, and HCT-116 in a dose-dependent manner. Cytological observations by an inverted phase contrast microscope and Hoechst 33342/PI dual-staining assay showed typical apoptotic morphology of cancer cells upon treatment with curzerenone and alismol. Both compounds induce apoptosis through the activation of caspase-3. It can thus be suggested that curzerenone and alismol are modulated by apoptosis via caspase-3 signalling pathway. The findings of the present study support the use of Curcuma zedoaria rhizomes in traditional medicine for the treatment of cancer-related diseases. Thus, two naturally occurring sesquiterpenoids, curzerenone and alismol, hold great promise for use in chemopreventive and chemotherapeutic strategies.