Abstract 3204: Screening of extracts from ethnopharmacologically selected peruvian plants in human hepatocarcinoma cell line Hep3B
Authors: Jean Edouard Gairin, Cedric Lavergne, Maelle Carraz, Valérie Jullian, Geneviève Bourdy, Michel Wright
Journal: Cancer Research (2014)

Abstract Liver cancer, for which hepatocellular carcinoma (HCC) represents the most frequent primitive form, is ranked sixth and third in terms of incidence and death respectively in the world. Its survival rate at 5 years is low (less than 10 %). There is no effective treatment to date, surgical approaches excepted or sorafenib with a gain in survival of 3 months. In view of this limitation of therapeutic alternatives, the search and identification of new molecules of natural origin remain an important issue. In this study, the pharmacological properties of 63 extracts, prepared from Peruvian plants selected upon ethnopharmacological investigations conducted in Peru, were analyzed. The extracts were tested in an in vitro phenotypic screening approach on the human hepatocellular carcinoma cell line, Hep3B, following a 3-step cell analysis: 1- the first step consisted in the determination of a screening score which was defined according to 3 criteria : APE, MIT and OMM. APE refers to the Anti-Proliferative Effect of the extract, MIT to the ability of the extract to modify the MITotic events (by increasing or decreasing the number of cells in mitosis), and OMM refers to the ability of an extract to induce Original Morphological Modifications to the treated cells. The score values ranged from 1 to 27 and a score value of 12 was defined as the threshold. Twenty five extracts exhibited a score value &amp;gt; 12 and were selected for further analysis. 2- the second step consisted in the determination of the cytotoxic effect of the 25 extracts selected from step 1, measured after a 48 hrs incubation time. Of these extracts, 11 showed IC50 values &amp;gt; 50 µg/ml, 10 with IC50 between 15 and 50 µg/ml and 4 with IC50 &amp;lt; 15 µg/ml The 14 extracts which exhibited IC50 values lower than 50 µg/ml were selected for the final step. 3- the third step consisted in studying the extracts inducing original phenotypic changes. This led to the selection of 4 extracts : 2 extracts of different families (Iridaceae and Asteraceae) induced blocking Hep3B cells in prometaphase while 2 other extracts, from the same genus (Asteraceae) induced cytoskeletal reorganization. This latter effect was original since it occurred on cells in interphase and not on mitosis as it can be seen with the classical tubulin inhibitors such as colchicine, vinblastine or paclitaxel. Interestingly, the plants from which come the 4 extracts inducing original phenotypes have been little studied so far either chemically or pharmacologically, suggesting that they may be a source of new molecules of therapeutic interest and/or with original structures. Citation Format: Jean Edouard Gairin, Cedric Lavergne, Maelle Carraz, Valérie Jullian, Geneviève Bourdy, Michel Wright. Screening of extracts from ethnopharmacologically selected peruvian plants in human hepatocarcinoma cell line Hep3B. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3204. doi:10.1158/1538-7445.AM2014-3204