The administration of demethyl fruticulin A from Salvia corrugata to mammalian cells lines induces "anoikis", a special form of apoptosis.
Recently demethyl fruticulin A was identified as the major diterpenoid component of the exudates produced by the trichomes of Salvia corrugata leafs. Given the documented apoptotic effects of some of the other known components of the exudates from Salvia species, we assessed if demethyl fruticulin A, once administered to mammalian cells, was involved in the onset of apoptosis and if its biological effects were exerted through the participation of a scavenger membrane receptor, CD36. Three model cell lines were chosen, one of which lacking CD36 expression. Functional availability of the receptor, or its transcriptional rate, were blocked/reduced with a specific antibody or by the administration of vitamin E. Immunodetection of cell cytoskeletal components and tunel analysis revealed that demethyl fruticulin A triggers the onset of anoikis, a special form of apoptosis induced by cell detachment from the substrate. Impairment of CD36 availability/transcription confirmed the receptor partial involvement in the intake of the substance and in anoikis, as also sustained by FACS analysis and by the downregulation of p95, a marker of anoikis, upon blockade of CD36 transcription. However, experiments with CD36-deficient cells suggested that alternate pathways, still to be determined, may take part in the biological effects exerted by demethyl fruticulin A.
Giannoni
Paolo
P
Stem Cell Laboratory, Advanced Biotechnology Center, Largo R. Benzi 10, 16132 Genova, Italy. paolo.giannoni@cba-biotecnologie.it
Narcisi
Roberto
R
De Totero
Daniela
D
Romussi
Giovanni
G
Quarto
Rodolfo
R
Bisio
Angela
A
D000818:Animals; D023102:Anoikis / Q000187:drug effects*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002521:Cercopithecus; D003599:Cytoskeleton / Q000187:drug effects; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000882:Haplorhini; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D020935:MAP Kinase Signaling System / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D051116:Receptors, Scavenger / Q000187:drug effects*; D027544:Salvia / Q000737:chemistry*; D014810:Vitamin E / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D018955:CD36 Antigens; D004224:Diterpenes; D010936:Plant Extracts; D051116:Receptors, Scavenger; C539555:demethylfruticuline A; D014810:Vitamin E