Nahed. El Najjar“Comparative Antitumor Effects of Extracts from Selected Indigenous Plants of Lebanon against Colon Cancer using in vitro and in vivo Models”, 2004
 
We have recently screened 109 crude extracts prepared from indigenous Lebanese plants for potential anticancer properties as part of our involvement in the Initiative of Biodiversity Studies in Arid Regions (ibsar). The aim of this study is to identify potential chemopreventive properties against colon cancer from three (Ep, Tf, and VL) of the four identified plant extracts using in vivo and in vitro models. Towards this end, we investigated the growth inhibitory and cytotoxic effects of the extracts on two normal mouse cell lines (Scp2 and ModeK) and on two human colon cancer cells (HCT- 116 and HT- 29). We also studied the effects of the extracts on cell cycle regulation and apoptosis signaling pathways in human colon cancer cells in an attempt to identify their mechanisms of antiproliferation and determined their colon cancer chemopreventive effects using the 1,2- dimethylhydrazine (DMH) mouse model of colon cancer. We show that the three extracts are non cytotoxic to normal cells and inhibit the growth of cancer cells in a dose- dependent manner. Flow cytometric analyses demonstrate that all extracts induce apoptosis at higher doses and S phase arrest at lower doses in HCT- 116 cells. We show that the p53 wild type HCT- 116 cells are more sensitive than p53 mutant HT- 29 cells to the proapoptotic effects of the plant extracts. Ep, Tf, and VL- mediated cell cycle arrest and/ or apoptosis is associated with their ability to induce the expression of p53 and p21 proteins and cause a significant increase in Bax/ Bcl- 2 ratio. In vivo, we demonstrate that the intraperitoneal (i. p.) injection of the undiluted crude water extracts for 10 consecutive days is not toxic to Balb/ c mice. All plant extracts, when injected i. p. during tumor initiation phase, significantly inhibit adenoma and adenocarcinoma development by an average of 65% at weeks 20 and 30. In addition, the extracts inhibit the numbers (Ep only) and the mean sizes of aberrant crypt foci (Ep, Tf and VL). These findings support a potential chemopreventive role of the indigenous Lebanese extracts Ep, Tf, and VL against colon cancer.