Anticancer activities of two sesquiterpene lactones, millerenolide and thieleanin isolated from Viguiera sylvatica and Decachaeta thieleana.
The present study was carried out in order to examine the anticancer properties of two sesquiterpene lactones, millerenolide and thieleanin, isolated from Viguiera sylvatica and Decachaeta thieleana, against cell lines in vitro, and on the growth B16/BL6 melanoma tumors in C57BL/6 mice. Millerenolide and thieleanin showed a similar pattern of cytotoxicity with the greatest effect on viability being evident with A549 human lung cancer cells (IC(50) - 40 and 32 microM respectively), and with the 3T3/HER2 cell line which are 3T3 mouse fibroblasts transfected with the HER2 oncogene (IC(50) - 16 and 28 microM respectively). The parent 3T3 cells and the B16/BL6 mouse melanoma cells were less sensitive to these compounds, with thieleanin showing an IC(50) with B16/BL6 greater than the highest dose tested (203 microM). Treatment with millerenolide (8 mg/kg, i.p. on days 0, 2 and 4 post-inoculation) 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 detectable tumor (millerenolide - day 15.2+/-0.4 vs control - day 12.8+/-0.5, mean+/-SEM, P=0.011). In contrast, treatment with thieleanin (8 mg/kg every other day up to the day of kill) neither retarded the appearance of the tumor nor its growth.
Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, Caracas 1020-A, Venezuela. ptaylor@ivic.ve
Peter G
PG
Taylor
Omar A
OA
Dupuy Loo
José A
JA
Bonilla
Renato
R
Murillo
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000627:therapeutic use*; D019659:Asteraceae / Q000737:chemistry; D045744:Cell Line, Tumor / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity
D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D016328:NF-kappa B; D010936:Plant Extracts; D012717:Sesquiterpenes; C532684:millerenolide; C533420:thieleanin