In vitro growth inhibitory effects of cytochalasins and derivatives in cancer cells.

Abstract

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.

• Authors: Gwendoline Van Goietsenoven, Véronique Mathieu, Anna Andolfi, Alessio Cimmino, Florence Lefranc, Robert Kiss, Antonio Evidente
• Journal: Planta medica (Planta Med) Vol. 77 Issue 7 Pg. 711-7 (May 2011) ISSN: 1439-0221 [Electronic] Germany
• PMID: 21058241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Antineoplastic Agents
• Cytochalasins

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Ascomycota (chemistry)
• Cell Line, Tumor
• Cytochalasins (chemistry, pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Mice
• Structure-Activity Relationship
• Tumor Cells, Cultured