Microtubule-interfering activity of parthenolide.
Parthenolide is an active sesquiterpene lactone present in a variety of medicinal herbs, well known as anti-inflammatory drug. It has recently been proposed as a chemotherapeutic drug, but the pharmacological pathways of its action have not yet been fully elucidated. Firstly, we explored whether the anticancer properties of parthenolide may be related to a tubulin/microtubule-interfering activity. We additionally compared bioactivities of parthenolide with those checked after combined treatments with paclitaxel in human breast cancer MCF-7 cells. Parthenolide exerted in vitro stimulatory activity on tubulin assembly, by inducing the formation of well-organized microtubule polymers. Light microscopy detections showed that parthenolide-induced alterations of either microtubule network and nuclear morphology happened only after combined exposures to paclitaxel. In addition, the growth of MCF-7 cells was significantly inhibited by parthenolide, which enhanced paclitaxel effectiveness. In conclusion, the antimicrotubular and antiproliferative effects of parthenolide, well known microtubule-stabilizing anticancer agent, may influence paclitaxel activity. The tubulin/microtubule system may represent a novel molecular target for parthenolide, to be utilized in developing new combinational anticancer strategies.
Miglietta
Antonella
A
Department of Experimental Medicine and Oncology, University of Torino, Corso Raffaello 30, 10125 Torino, Italy. antonella.miglietta@unito.it
Bozzo
Francesca
F
Gabriel
Ludovica
L
Bocca
Claudia
C
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D045744:Cell Line, Tumor; D003078:Colchicine / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology*; D020903:Tanacetum parthenium / Q000737:chemistry*; D014404:Tubulin / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012717:Sesquiterpenes; D014404:Tubulin; C002669:parthenolide; D017239:Paclitaxel; D003078:Colchicine