4'-methoxy-2-styrylchromone a novel microtubule-stabilizing antimitotic agent.
4'-methoxy-2-styrylchromone, a new synthetic chromone was identified as a selective proliferation inhibitor of human tumor (MCF-7 and NCI-H460) cell lines than to non-tumor cells (MRC-5). The antiproliferative activity of this chromone was also extensive to peripheral human lymphocytes. 4'-Methoxy-2-styrylchromone was found to block tumor cells in the G2/M phase of the cell cycle. The G2/M arrest of NCI-H460 cells was dose- and time-dependent, reaching a maximum after 12-h treatment while MCF-7 cells reached the maximum value of G2/M accumulation only after a 24-h treatment. Chromone-treated cells evidenced a high frequency of cells in prometaphase, indicating progression beyond G2 and arrest early in mitosis. This mitotic arrest was associated with abnormal mitotic spindles characterized by the formation of a monopolar structure, suggesting that the chromone interferes with microtubules. The results of an in vitro tubulin polymerization assay showed that this chromone stabilizes microtubules in a manner similar to paclitaxel.
CEQOFFUP-Centro de Estudos de Química Orgânica, Fitoquímica e Farmacologia da Universidade do Porto, Porto, Portugal.
Joana
J
Marinho
Madalena
M
Pedro
Diana C G A
DC
Pinto
Artur M S
AM
Silva
José A S
JA
Cavaleiro
Claudio E
CE
Sunkel
Maria São José
MS
Nascimento
D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002867:Chromones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects*; D008940:Mitotic Index; D015394:Molecular Structure; D013343:Styrenes / Q000737:chemistry / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
C528112:4'-methoxy-2-styrylchromone; D002867:Chromones; D013343:Styrenes; D050257:Tubulin Modulators