Evaluation of the anticancer activities of two sesquiterpene lactones, millerenolide and thieleanin, isolated from plants of the Asteraceae family

Abstract

We studied the anticancer properties of two sesquiterpene lactones, millerenolide (a germacranolide) and thieleanin (a guaianolide) both in vitro and in vivo. They were isolated from two plants of the Asteraceae family which is known for its anti-inflammatory properties [1]. These lactones showed a similar pattern of cytotoxicity in A549 human lung cancer cells and in 3T3/HER2 cells (3T3 cells transfected with the HER2 oncogene). The parent 3T3 cells and the B16/BL6 mouse melanoma cells were less sensitive to these compounds. Treatment with millerenolide (8mg/kg, i.p. days 0, 2 and 4 postinoculation) significantly inhibited the growth of subcutaneous B16/BL6 tumors in C57BL/6 mice (50% inhibition at day 25, P =0.015), as well as retarding the appearance of a detectable tumor (millerenolide – day 15.2±0.4 vs. control – day 12.8±0.5, P=0.011). In contrast, treatment with thieleanin neither retarded the appearance of the tumor nor its growth. This is one of the first demonstrations of an anticancer effect of a sesquiterpene lactone in vivo and we propose that this effect may be due to mechanisms other than direct cytotoxicity [2].