Bioactive
compounds from the medicinal plant, Eurycoma
longifolia Jack have been shown to promote anti-proliferative effects on
various cancer cell lines.
Here
we examined the effects of purified eurycomanone, a quassinoid found in Eurycoma longifolia Jack extract, on the expression of
selected genes of the A549 lung cancer cells.
Eurycomanone inhibited A549 lung cancer cell
proliferation in a dose-dependent manner at concentrations ranging from 5 to
20μg/ml.
The
concentration that inhibited 50% of cell growth (GI(50)) was 5.1μg/ml. The
anti-proliferative effects were not fully reversible following the removal of
eurycomanone, in which 30% of cell inhibition still remained (p<0.0001,
T-test). At 8μg/ml (GI(70)), eurycomanone suppressed anchorage-independent
growth of A549 cells by >25% (p<0.05, T-test, n=8) as determined using
soft agar colony formation assay.
Cisplatin,
a chemotherapy drug used for the treatment of non small cell lung cancer on the other hand, inhibited A549 cells
proliferation at concentrations ranging from 0.2μg/ml to 15μg/ml with a GI(50)
of 0.58μg/ml. The treatment with eurycomanone reduced the abundance expression
of the lung cancer markers, heterogeneous nuclear
ribonucleoprotein (hnRNP) A2/B1, p53 tumor suppressor protein and other cancer-associated genes including prohibitin (PHB),
annexin 1 (ANX1) and endoplasmic reticulum protein 28 (ERp28) but not the house
keeping genes. The mRNA expressions of all genes with the exception of PHB were
significantly downregulated, 72h after treatment (p<0.05, T-test, n=9).
These
findings suggest that eurycomanone at viable therapeutic concentrations of
5-20μg/ml exhibited significant anti-proliferative and anti-clonogenic cell
growth effects on A549 lung cancer cells. The
treatment also resulted in suppression of the lung cancer
cell tumor markers and several known cancer cell
growth-associated genes.
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