12-Deoxyphorbol 13-palmitate mediated cell growth inhibition, G2-M cell cycle arrest and apoptosis in BGC823 cells.

The highly toxic monomer 12-deoxyphorbol 13-palmitate (G) was extracted from the roots of Euphorbia fischeriana. Our experimental data confirmed studies showing that 12-deoxyphorbol 13-palmitate had certain antitumor activities. The MTT method, soft agar experiments, and nude mouse tumor experiments proved that 12-deoxyphorbol 13-palmitate inhibited the growth of BGC823 cells. We found that the drug could induce cell cycle arrest at the G2-M checkpoint in BGC823 cells. The compound also induced apoptosis as assayed by Annexin-V-FITC/PI dual labeling, AO/EB dyeing, and caspase-3 and caspase-9 activity. The reduction in expression of cyclin B1 protein and the increased activity of reactive oxygen species were observed in BGC823 cells treated with 12-deoxyphorbol 13-palmitate for 24 h. In addition, we found down-regulation of cdc2/cyclin B, cyclin A and p-chk1 in tumor cells. There was also up-regulation of Bax, p53, p21, and IκB-α and down-regulation of Bcl-2 and NF-κB by WB. Our studies may define a novel mechanism by which 12-deoxyphorbol 13-palmitate inhibits tumor cell growth and induces apoptosis. The results of our current studies provided strong experimental evidence for the use of 12-deoxyphorbol 13-palmitate as a potential preventive and/or therapeutic agent in cancer.