Abstract 2188: Isolation and anticancer properties of some naturally occurring sesquiterpene lactones from Pulicaria undulate
Authors: Mohammed M. Arab, Fahad A. Al-Abbasi, Mohamed-Elamir F. Hegazy, Ali M. El-Halawany, Ahmed M. Al-Abd
Journal: Cancer Research (2016)

Abstract Sesquiterpene lactones are natural compounds abundant in several plant families with a variety of biological activities such as antitumor effects. Camptothecin is famous topoisomerase interactive agent with anticancer properties against several types of malignancies. The purpose of this study is to investigate the potential chemotherapeutic effects of some naturally occurring sesquiterpene lactones isolated from Pulicaria undulate. Compounds with promising anticancer profile has been further investigated for potential chemomodulatory effects to camptothecin in different tumor cell types. Cytotoxicity of the isolated terpenoids were assessed against human breast adenocarcinoma (MCF7), human colorectal cancer (HCT116 and LS174T) and human hepatocellular carcinoma (HepG2) cells using sulpharhodamine-B assay after cell exposure for 72 h. Cytotoxic parameters (IC50 and R-fraction) were calculated from cell viability after fitting using Emax model. Two sesquiterpene lactones, 2α-hydroxy alantolactone and tomentosin, showed considerable cytotoxic profile against cell lines under investigation with IC50's ranging from 5 to 22 μM and from 14 to 39 μM, respectively. Treatment with camptothecin alone showed significant cytotoxicity with IC50's range from 0.13 to 1.5 μM in the same panel of cell lines. Equitoxic combination of tomentosin with camptothecin (combination ratio was 1:100) resulted in 60% reduction for the IC50 of camptothecin alone in HCT116 cells. On the other hand, equitoxic combination for hydroxy alantolactone with camptothecin did not significantly enhance the cytotoxicity of camptothecin against HCT116 cells. To explain the interactive characteristics of hydroxy alantolactone and tomentosin with camptothecin, annexin-V/PI staining coupled with flow cytometry analysis for apoptosis and necrosis was assessed after treatment with camptothecin alone or in combination with hydroxy alantolactone or tomentosin. Again, tomentosin combination with camptothecin significantly increased apoptotic as well as necrotic cell populations compared to camptothecin treatment alone by 2-3 folds. On the other hand, combination of camptothecin with hydroxy alantolactone significantly increased apoptotic cell population with reciprocal decrease in necrotic cell population. In conclusion, hydroxy alantolactone and tomentosin might be promising anticancer agents. However, further molecular investigation is required to understand the nature of interaction between the isolated sesquiterpene lactones and cornerstone chemotherapeutics such as camptothecin. Citation Format: Mohammed M. Arab, Fahad A. Al-Abbasi, Mohamed-Elamir F. Hegazy, Ali M. El-Halawany, Ahmed M. Al-Abd. Isolation and anticancer properties of some naturally occurring sesquiterpene lactones from Pulicaria undulate. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2188.