Sesquiterpenes as immunosuppressants.
BACKGROUND
The search for new immunosuppressive drugs is a high priority. Sesquiterpenes constitute a family of compounds with a great variety of biological activities due to their reactive moieties.


METHODS
Human tumor cell lines and murine primary cells and human peripheral blood mononuclear cells or primary CD4+ cells from healthy individuals were stimulated in the presence of sesquiterpenes. Cell division was analyzed by 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester, cell cycle progression by Hoecht, and cell death by Anexin-V and propidium iodine staining. Cytokine secretion was analyzed by means of a bioplex assay.


RESULTS
Two sesquiterpene derivatives of the 18 previously shown to inhibit vegetal cell growth are shown to block cell division and cell cycle progression in human and murine cell lines and primary cells. Cytokine secretion is also impaired on stimulation in the presence of sesquiterpenes.


CONCLUSIONS
Here, we show that sesquiterpenes heliannuols constitute a novel family of molecules with potential use as immunosuppressants. Moreover, we show that an assay based on the allelopathic effect of plant leads can be used as a cost-effective screening previous to studies in mammalian cells.
Munoz-Suano
Alba
A
Departamento de Bioquímica y Biología Molecular (Inmuologia), Universidad de Cadiz, Hospital Universitario de Puerto Real, Unidad de Investigación, Carretera NIV Km665, 11510 Puerto Real, Cadiz, Spain.
Chinchilla
David
D
Aguilar
Susana
S
Molinillo
Jose M G
JM
Macias
Francisco A
FA
Rodríguez-Iglesias
Manuel A
MA
Garcia-Cozar
Francisco
F
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006368:Helianthus; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019169:Jurkat Cells / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010936:Plant Extracts / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000494:pharmacology*
D015704:CD4 Antigens; D016207:Cytokines; D007166:Immunosuppressive Agents; D010936:Plant Extracts; D012717:Sesquiterpenes