Combination of phenylpropanoids with 5-fluorouracil as anti-cancer agents against human cervical cancer (HeLa) cell line

Abstract

Combination therapy is the most effective treatment strategy in cancer to overcome drug toxicity and drug induced resistance. The effect of eight phenylpropanoids in combination with 5-fluorouracil against the cervical cancer cells (HeLa) is reported here. The cytotoxic activity of these phenylpropanoids against HeLa cells is in the order of eugenol>ferulic>cinnamic>caffeic>chlorogenic>p-coumaric>3,4-dimethoxycinnamic>2,4,5-trimethoxycinnamic acids. Eugenol, ferulic and caffeic acids interacted synergistically with the drug, in bringing about a reduction in the amount of the latter. Flow cytometry results indicated that the combination of eugenol and 5-fluorouracil increased the number of cells in the S and G2/M phases when compared to treatment with the individual compounds alone. This indicates that they possess different cell cycle targets and induce apoptosis in the cancer cells. In vitro hemolytic activity of phenylpropanoids on human erythrocytes showed that the compounds possessed minimum amount of hemolytic activity, indicating that they can be used as drugs without causing adverse toxicity. 3D-quantitative structure activity relationship studies indicate the importance of electrostatic region near the substitutions present in the benzene ring and near the double bond of the compounds for anticancer and hemolytic activities, respectively. The models derived had good statistical predictive capability.