[Show abstract][Hide abstract] ABSTRACT: A subpopulation of cancer stem cells is recognized as the cause of tumorigenesis and spreading. To investigate the effects
of casticin (5,3′-dihydroxy-3,6,7,4′-tetramethoxyflavone), derived from Fructus Viticis Simplicifoliae, on lung cancer stem cells, we isolated and identified a subpopulation of lung cancer stem-like cells (LCSLCs) from non-small-cell
lung carcinoma A549 cells with the features including self-renewal capacity and high invasiveness in vitro, elevated tumorigenic activity in vivo, and high expression of stemness markers CD133, CD44, and aldehyde dehydrogenase 1 (ALDH1), using serum-free suspension sphere-forming
culture method. We then found that casticin could suppress the proliferation of LCSLCs in a concentration-dependent manner
with an IC50 value of 0.4 μmol/L, being much stronger than that in parental A549 cells. In addition, casticin could suppress the self-renewal
and invasion of LCSLCs concomitant with decreased CD133, CD44, and ALDH1 protein expression and reduced MMP-9 activity. Further
experiments showed that casticin suppressed self-renewal and invasion at least partly through down-regulation of Akt phosphorylation.
In conclusion, casticin suppressed the characteristics of LCSLCs, suggesting that casticin may be a candidate compound for
curing lung cancer via eliminating cancer stem cells.
Preview · Article · Nov 2013 · Acta Biochimica et Biophysica Sinica
[Show abstract][Hide abstract] ABSTRACT: Genistein, 5,7,4'-trihydroxylisoflavone, a major component of soybean products, has been reported to possess anticancer activities. We examined the antitumor effects of 7-difluoromethoxyl-5,4'-di-n-octylgenistein (DFOG), a novel synthetic genistein derivative, on human ovarian cancer cells as well as the molecular mechanism. The growth-inhibitory effects of genistein and DFOG were determined using MTT assay and clonogenic assay in CoC1 and SKOV3 human ovarian cancer cells. Apoptotic activities of DFOG were observed using histone/DNA ELISA assay and flow cytometry with propidium iodide (PI) staining. Multiple molecular techniques, such as RT-PCR, western blot analysis, siRNA and cDNA transfection were used to explore the molecular mechanism. We demonstrated that nine of the genistein derivatives had a more effective antitumor activity than genistein. Among the afore-mentioned derivatives, DFOG presented with the strongest activity against CoC1 and SKOV3 cells in vitro. DFOG and genistein inhibited the growth of CoC1 and SKOV3 cells, accompanied by cell cycle arrest in the G2/M phase. DFOG caused apoptotic cell death with concomitant attenuation of Forkhead box protein M1 (FoxM1) and its downstream genes, such as survivin, cdc25B, cyclin B, and increased p27KIP1. Downregulation of FoxM1 by siRNA followed by DFOG treatment resulted in enhanced cell growth inhibition and induction of apoptosis. Upregulation of FoxM1 by cDNA transfection attenuated DFOG-induced cell growth inhibition and apoptotic cell death. Our results show that the molecular role of FoxM1 in mediating the biological effects of DFOG and genistein in human ovarian cancer cells suggests that FoxM1 could be a novel target for the treatment of human ovarian cancer.