In vitro growth inhibitory effects of cytochalasins and derivatives in cancer cells.
The in vitro anticancer activity of eight natural cytochalasins and three hemisynthetic derivatives of cytochalasin B on six cancer cell lines was evaluated. The IC (50) in vitro growth inhibitory concentrations, as determined by an MTT colorimetric assay, ranged between 3 and 90 µM and did not relate to the intrinsic sensitivity of the cancer cell lines to proapoptotic stimuli. Structure activity relationship (SAR) analyses revealed that the presence of an unmodified hydroxyl group at C-7 of the perhydroisoinsolyl-1-one residue as well as the functionalities and the conformational freedom of the macrocycle are all important features for cytochalasin-mediated anticancer activities in vitro. Computer-assisted phase-contrast microscopy revealed two groups of cytochalasins, i.e., cytotoxic versus cytostatic ones. Our data open new possibilities for tuning cytochalasin targets and developing nontoxic, cytostatic cytochalasins to combat cancers associated with poor prognoses, such as those that display intrinsic resistance to proapoptotic stimuli.
Laboratoire de Toxicologie, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
Gwendoline
G
Van Goietsenoven
Véronique
V
Mathieu
Anna
A
Andolfi
Alessio
A
Cimmino
Florence
F
Lefranc
Robert
R
Kiss
Antonio
A
Evidente
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry; D045744:Cell Line, Tumor; D003572:Cytochalasins / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003572:Cytochalasins