title: Rac-dependent doubling of HeLa cell area and impairment of cell migration and cell cycle by compounds from Iris germanica.
abstract: Plants are an infinite source of bioactive compounds. We screened the Israeli flora for compounds that interfere with the organization of the actin cytoskeleton. We found an activity in lipidic extract from Iris germanica that was able to increase HeLa cell area and adhesion and augment the formation of actin stress fibers. This effect was not observed when Ref52 fibroblasts were tested and was not the result of disruption of microtubules. Further, the increase in cell area was Rac1-dependent, and the iris extract led to slight Rac activation. Inhibitor of RhoA kinase did not interfere with the ability of the iris extract to increase HeLa cell area. The increase in HeLa cell area in the presence of iris extract was accompanied by impairment of cell migration and arrest of the cell cycle at G1 although the involvement of Rac1 in these processes is not clear. Biochemical verification of the extract based on activity-mediated fractionation and nuclear magnetic resonance analysis revealed that the active compounds belong to the group of iridals, a known group of triterpenoid. Purified iripallidal was able to increase cell area of both HeLa and SW480 cells.
authors.affiliation: The Institute of Plant Sciences, Volcani Center, P.O. Box 6, Bet-Dagan, 50250, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Halpert
authors.forename: Mohamad
authors.initials: M
authors.lastname: Abu-Abied
authors.forename: Dror
authors.initials: D
authors.lastname: Avisar
authors.forename: Yoni
authors.initials: Y
authors.lastname: Moskovitz
authors.forename: Osnat
authors.initials: O
authors.lastname: Altshuler
authors.forename: Avner
authors.initials: A
authors.lastname: Cohen
authors.forename: Mira
authors.initials: M
authors.lastname: Weissberg
authors.forename: Joseph
authors.initials: J
authors.lastname: Riov
authors.forename: Hugo E
authors.initials: HE
authors.lastname: Gottlieb
authors.forename: Avichai
authors.initials: A
authors.lastname: Perl
authors.forename: Einat
authors.initials: E
authors.lastname: Sadot
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology; D008841:Actin Cytoskeleton / Q000187:drug effects*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects*; D048429:Cell Size; D003511:Cyclohexanols / Q000302:isolation & purification / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints; D006367:HeLa Cells; D006801:Humans; D031323:Iris Plant / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D027343:Rhizome / Q000737:chemistry; D014162:Transfection; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: C439953:26-hydroxy-22-methylcycloirid-16-enal; D000577:Amides; D003511:Cyclohexanols; D010936:Plant Extracts; D011725:Pyridines; C107953:RAC1 protein, human; D014315:Triterpenes; C473636:iridal; C066737:RHOA protein, human; C108830:Y 27632; D000171:Acrolein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein