Linalool and eugenol exhibit apoptotic potential on hela and caco-2 cells through the modulation of src kinases and ADAMTS proteases while only eugenol displays anti-angiogenic features on HeLa cells

The cytotoxic effects of linalool and eugenol on HeLa and Caco-2 cancer cells were investigated. The expression of the Fyn, Hck, and ADAMTS genes and Bcl-2, Bax, VEGF proteins were determined through the real-time-qPCR and Western blot analysis, respectively. IC50 values of linalool on HeLa cell were 799.6, 1228, and 1239 mu g/mL after 24, 48, and 72 h, respectively, whereas those of eugenol were 388, 94.35, and 73.78 mu g/mL. IC50 values in Caco-2 cells were 887.7, 1259, and 1356 mu g/mL for linalool whereas those of eugenol were 452.7, 578.3, and 433.3 mu g/mL after 24, 48, and 72 h, respectively. As a control, Hek-293 IC50 values were 1047 and 556.7 mu g/mL for linalool and eugenol, respectively. Linalool at 1024 mu g/mL concentration increased Bax and Bcl-2 levels significantly in both cell lines (p < 0.001). However, eugenol treatment did not alter Bax levels (p > 0.05), but it decreased Bcl-2 levels significantly (p < 0.001). Additionally, 1024 mu g/mL linalool exposure increased Fyn gene expression in Caco-2 cells, which was not observed for HeLa cells. Unlike linalool, eugenol upregulated ADAMTS1 gene expression and decreased VEGF levels in HeLa cells. On the contrary, in Caco-2 cells, eugenol treatment did not affect ADAMTS1 levels, whilst linalool upregulated ADAMTS1 levels, especially at 1024 mu g/mL concentration. VEGF levels increased in Caco-2 cells following eugenol treatment. ADAMTS3 levels decreased in Caco-2 cells with exception of 1024 mu g/mL linalool treatment. These results indicated the anti-proliferative, apoptotic effects of plant-derived natural compounds. It is also revealed that eugenol might also display antiangiogenic properties on HeLa cells in addition to its apoptotic effects.