Triggering of Apoptosis and Cell Cycle Arrest by Fennel and Clove Oils in Caco-2 Cells: the Role of Combination

Fennel () and clove () oils are known for their various biological effects, including anticancer properties. To investigate the anticancer effect of combined fennel and clove oil treatment on Caco-2 cells and normal human lymphocytes (NHL). GC-MS, cytotoxicity, morphological, apoptosis-related marker, and flow cytometric cell cycle distribution analyses were conducted. Seventeen volatile compounds were identified in fennel oil, including -anethole (68.3%) and (+)-fenchone (8.1%). In clove oil, 22 compounds, including eugenol (71.4%) and caryophyllene (8.7%), were identified. IC of the fennel, clove, and oil mixture were 300 ± 5.0, 150 ± 4.0, and 73 ± 2.5 µg/mL, respectively with combination index (CI) < 1.0. Mechanistic anticancer properties were investigated using 30, 45, and 60 µg/mL oil mixture. Analysis of apoptotic morphology, flow cytometric cell cycle distribution, and apoptosis-related markers, such as Bcl-2 and Ki-67, confirmed cell cycle arrest and apoptosis induction in Caco-2 cells by the fennel and clove oil combination. Moreover, the oil mixture did not exert significant ( < 0.01) toxicity on NHL The oil mixture exerted selective cytotoxicity towards Caco-2 cells through cell cycle arrest and apoptosis, which may occur through synergistic effects between fennel and clove oil active ingredients.