Indoloquinolizidine derivatives as novel and potent apoptosis inducers and cell-cycle blockers.
A collection of approximately 11 000 natural-product derived and inspired compounds was screened for potential apoptosis inducers in the human tumour cell lines HepG2 (liver), HeLa (cervix) and MCF-7 (breast) by means of MTT and ATP-luminescence assays, automated cell counting, caspase 3/7 assay as well as by fluorescence activated cell sorting (FACS) analysis. A group of seven indoloquinolizidine derivatives was identified that exhibited IC(50) values for cell proliferation as low as 2 mumol L(-1), with no major necrosis of cells detectable. At the same time, an increase in the rate of apoptosis of up to 600 % relative to the reference level was observed. FACS analysis indicated that these effects are related to an arrest of cells in the G(2)M phase of the cell cycle.
Wehner
Frank
F
Department of Systemic Cell Biology, Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
Nören-Müller
Andrea
A
Müller
Oliver
O
Reis-Corrêa
Ivan
I
Giannis
Athanassios
A
Waldmann
Herbert
H
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D054837:Quinolizidines / Q000737:chemistry / Q000494:pharmacology*
D007211:Indoles; D054837:Quinolizidines