Altholactone Induces Apoptotic Cell Death in Human Colorectal Cancer Cells
Article first published online: 22 NOV 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Volume 26, Issue 6, pages 926–931, June 2012
How to Cite
Mhaidat, N. M., Abdul-Razzak, K. K., Alkofahi, A. S., Alsarhan, A. M., Aldaher, A. N. and Thorne, R. F. (2012), Altholactone Induces Apoptotic Cell Death in Human Colorectal Cancer Cells. Phytother. Res., 26: 926–931. doi: 10.1002/ptr.3666
- Issue published online: 4 JUN 2012
- Article first published online: 22 NOV 2011
- Manuscript Accepted: 29 AUG 2011
- Manuscript Revised: 5 AUG 2011
- Manuscript Received: 14 APR 2011
- Jordan University of Science and Technology, Irbid, Jordan. Grant Number: 186/2008
- colorectal cancer;
- apoptosis, caspase-4;
- reactive oxygen species
Resistance of colorectal cancer (CRC) to the available chemotherapy reveals the demand for identification of new anticancer agents. We evaluated the antitumour potential of altholactone, a naturally occurring bioactive compound isolated from Goniothalamus spp. (Annonaceae) hooks, against CRC cells. Antitumour activity of altholactone was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the propidium iodide method. Apoptosis mediators involved were assessed using biochemical inhibitors and Western blotting analysis. Results revealed that altholactone induced varying degrees of apoptosis in CRC cells but not in normal fibroblasts. Dissection of the altholactone-induced apoptotic signalling pathway revealed that altholactone activated caspase-dependent and -independent apoptotic pathways. Activation of caspase-4 appeared to be the initiating event in the caspase-dependent apoptotic pathway. Pre-treatment of CRC cells with the antioxidant N-acetylcysteine (NAC) significantly inhibited activation of caspase-4 and altholactone-induced apoptosis. These results indicate that altholactone induces selective cytotoxicity against colon carcinoma cells and warrants further clinical evaluation. Copyright © 2011 John Wiley & Sons, Ltd.