Cytotoxic activity of semi-synthetic ingenol derived from Euphorbia tirucalli on a large panel of human cancer cell lines.

Abstract

e13559 Background: The latex from Euphorbia tirucalli is used in Brazil as anticancer and other disease as folk treatment; however, little is known about its anticancer proprieties. We report in vitro activity of 3 semi-synthetic ingenol compounds derived from E. tirucalli, ingenol A (ingenol-3-trans-cinnamate), ingenol B (3-caproyl-ingenol) and ingenol C (ingenol-3-dodecanoate), against a large panel of human cancer cell lines. Methods: Anti-tumor effects of the 3 semi-synthetic compounds were assessed using MTS assays on 77 cancer lines from 13 tumor models, such as breast, colon, bladder, prostate, lung, pancreas, esophagus, glioblastoma, melanoma, head and neck and cervical cancer. Additionally, we evaluate the its potential combinatorial value with temozolomide (TMZ) in gliomas. Ongoing experiments will identify potential drug target(s) by assessing changes in global protein expression. Results: Ingenol A, B and C exhibited dose-dependent and time-dependent cytotoxic effects. Amongst the derived tested, ingenol C displayed the best activity across the tumor cell lines. In comparison with TMZ, ingenol C showed a median of 136 fold higher efficacy, range 15-511 fold, in the glioma cell lines analyzed. Conclusions: The semi-synthetic ingenol compounds, in particular the ingenol C, demonstrated a potent anti-tumor activity on all cancer cell lines evaluated. Our findings may provide insight into designing ingenol-based therapies for cancer patients. [Table: see text]