Monoterpenes have been identified as responsible of important therapeutic effects of plant-extracts. In this work, we try to compare the cytotoxic effect of six monoterpenes (carvacrol, thymol, carveol, carvone, eugenol and isopulegol) as well as their molecular mechanisms. The in vitro antitumor activity of the tested products, evaluated against five tumor cell lines, show that the carvacrol is the most cytotoxic monoterpene. The investigation of an eventual synergistic effect of the six natural monoterpenes with two anticancer drugs revealed that there is a significant synergy between them (p<5%). On the other hand, the effect of the tested products on cell cycle progression was examined by flow cytometry after DNA staining in order to investigate the molecular mechanism of their cytotoxic activity. The results revealed that carvacrol and carveol stopped the cell cycle progression in S phase; however, thymol and isopulegol stopped it in G0/G1 phase. Regarding carvone and eugenol, no effect on cell cycle was observed.

This investigation aimed to evaluate the in vitro and in vivo antitumor potential of a Moroccan propolis extracts. For in vitro assays, three mammalian tumor cell lines were used: BSR (hamster renal adenocarcinoma), Hep-2 (human laryngeal carcinoma) and P815 (murin mastocytoma). The propolis ethanolic extract as well as the ethyl acetate extract, exert an in vitro cytotoxic activity in dose-dependent manner. The IC50 values were ranging from 15 µg/mL to 38 µg/mL. This activity depends not only on the extract's chemical composition (analysed by HPLC/ESI-MS), but also on the target tumor cells. Interestingly, the cytotoxic effect of these extracts on the normal human peripheral blood mononuclear cells (PBMC) was weak when compared to that induced on tumor cells. On the other hand, oral route treatment of P815 tumor-bearing mice (DBA2/P815) with propolis ethanolic extract (5 mg per mouse every fourth day, five times for group A, and 2.5 mg per mouse every fourth day, five times for group B) significantly reduced the tumor volume (1.2 cm³ for group A and 2.7 cm³ for group B at the 22nd day after tumor graft). These effects are statistically significant as compared to those obtained with the control untreated mice (tumor volume 3.5 cm³ at day 22).