Effects of natural prenylated flavones in the phenotypical ER (+) MCF-7 and ER (-) MDA-MB-231 human breast cancer cells.
The effect of seven natural prenylated flavones in DNA synthesis of two human breast cancer cell lines, the estrogen-dependent ER (+) MCF-7 and the estrogen-independent ER (-) MDA-MB-231 cells, was evaluated. Flavones with an isopentenyl group at C-8 and a ring linking C-3 and C-2' presented a biphasic effect in DNA synthesis of ER (+) MCF-7 and displayed a stimulation at low concentrations (0.02-0.78 microM) whilst at higher concentrations (> 3.12 microM) inhibition was observed. No stimulation was observed in ER (-) MDA-MB-231. In contrast, all the flavones exhibited an antiproliferative effect in both ER (-) and ER (+). Curiously, the inhibition of DNA synthesis was accompanied by a high capacity of these cells to reduce MTT, which was concurrent with the appearance of an intense intracytoplasmic vacuolization. The accumulation of the formazan product in these vacuoles could justify the enhancements of MTT reduction. The characterization of these vacuoles with the autophagic marker monodansylcadaverine (MDC) is consistent with autophagic vacuoles, which led to the suggestion that these flavones could induce autophagy in both ER (+) and ER (-) breast cancer cell lines.
Pedro
Madalena
M
CEQOFFUP-Centro de Estudos de Química Orgânica, Fitoquímica and Farmacologia da Universidade do Porto, Portugal.
Lourenço
Cátia F
CF
Cidade
Honorina
H
Kijjoa
Anake
A
Pinto
Madalena
M
Nascimento
Maria São José
MS
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D013329:Structure-Activity Relationship; D014617:Vacuoles / Q000187:drug effects / Q000473:pathology
D004273:DNA, Neoplasm; D047309:Flavones; D011960:Receptors, Estrogen