The apoptotic effects of the flavonoid N101-2 in human cervical cancer cells.
ABSTRACT This study evaluated the anti-cancer effects of a naringenin derivative in human cervical cancer cells. In this study, a synthesized naringenin derivative, diethyl 5,7,4'-trihydroxy flavanone N-phenyl hydrazone (N101-2), inhibited cervical cancer cell growth, whereas naringenin itself exhibited no anti-cancer activity. N101-2 treatment inhibited cancer cell viability in a dose- and time-dependent manner through cell cycle arrest at sub-G1 phase, accompanied by an increase in apoptotic cell death. Expression of cyclins and ppRB was down-regulated, whereas that of CDK inhibitors and p53 increased upon N101-2 treatment. Meanwhile, we detected processing of caspases-8, -9, and -3, cleavage of PARP, as well as Bax up-regulation, which indicates activation of mitochondria-emanated intrinsic apoptosis signaling. Treatment with caspase-8 and -3 inhibitors also recovered cell cycling, and Fas/FasL expression increased in N101-2-treated cervical cancer cells, suggesting that Fas-mediated extrinsic apoptosis signaling was also activated. The tumor suppressor PTEN and its upstream regulator PPARγ were up-regulated with coincident inhibition of PI3K and phospho-Akt after N101-2 treatment. Taken together, we could conclude that N101-2 induces apoptosis by arresting the cell cycle at sub-G1 phase, activating mitochondria-emanated intrinsic and Fas-mediated extrinsic signaling pathways, and inhibiting the PI3K/AKT pathway in CaSki and SiHa human cervical cancer cells.
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ABSTRACT: The flavonoids found in many foods may have a protective effect against human gastric cancer. However, little information is available concerning the effects of flavonoids on the SGC-7901 cell line. Therefore, we first evaluated the effects of purified Flos Albiziae flavonoids (FAFs) on the proliferation of the SGC-7901 human gastric cancer cell line and investigated its possible anti-proliferative mechanisms. When SGC-7901 cells were treated with FAFs for various time periods (12-72 h) and at various doses (0-32 μg/ml), cell growth decreased significantly in a time- and dose-dependent manner. Morphological observations with fluorescence microscopy and transmission electron microscopy (TEM) yielded clear evidence of cell shrinkage, formation of cytoplasmic filaments, condensation of nuclear chromatin, and cell apoptosis in the presence of FAFs. Treatment with FAFs changed the expression levels of Bcl-2, P65, Bax and caspase. The anti-apoptotic protein expression of Bcl-2 and p65 decreased gradually with the increase in FAF concentration, compared with control cells (P<0.05). FAFs contributed to the increase in Bax and caspase expression. The expression of pro-apoptotic proteins Bax and caspase were upregulated by FAFs compared with control cells (P<0.01). These results demonstrated that FAFs effectively induced apoptosis in the SGC-7901 cell line. This indicates that FAFs are likely to possess anticancer activity.Experimental and therapeutic medicine 01/2013; 5(1):51-56. · 0.34 Impact Factor