The apoptotic effects of the flavonoid N101-2 in human cervical cancer cells

Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea.
Toxicology in Vitro (Impact Factor: 2.9). 10/2011; 26(1):67-73. DOI: 10.1016/j.tiv.2011.10.012
Source: PubMed


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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    • "Thereby, DHC and fisetin induced apoptosis, but not accelerated senescence in prostate cells (Haddad 2008). The study on diethyl 5,7,4 0 -trihydroxy flavanone N-phenyl hydrazone (N101-2), a synthesized naringenin derivative exhibited cervical cancer cell growth inhibition by arresting the cell cycle at sub-G1 phase, activating mitochondriaemanated intrinsic and Fas-mediated extrinsic signaling pathways, and inhibiting the PI3K/AKT pathway in CaSki and SiHa human cervical cancer cells (Kim et al. 2012). "
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    12/2013; 3(6). DOI:10.1007/s13205-013-0117-5
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    • "The results showed that FAFs inhibited the growth of those cancer cells in a concentration- and time-dependent manner. This was consistent with previous reports stating that flavonoids result in the inhibition of proliferation of human hepatocellular carcinoma cells in a dose- and time-dependent manner (17,18). "
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    ABSTRACT: Background: The globular heads of the human C1q receptor (gC1qR) are multi-compartmental and multi-functional cellular proteins. The list of biological responses mediated by the gC1qR includes growth perturbation and morphological abnormalities, along with the initiation of apoptosis. However, the effects of the gC1qR on the apoptosis of cervical squamous carcinoma cells (C33a and SiHa) have not been demonstrated. Methods: Here, human cervical tissues were examined for the expression of the gC1qR using real-time PCR and Western blot analysis. Apoptotic death of C33a and SiHa cells was assessed by flow cytometric analysis to detect the subG1 population. Viability, migration and proliferation of C33a and SiHa cells were detected via the water-soluble tetrazolium salt (WST-1) assay, the Transwell assay and the (3)H-thymidine incorporation into DNA assay ((3)H-TdR), respectively. Results: These data showed that expression of the gC1qR protein was significantly decreased in human cervical squamous cell carcinoma tissues relative to normal cervix tissues. C33a and SiHa cells transfected with a GFP-gC1qR vector resulted in the up-regulation of cellular apoptosis and an apparent increase in the expression of the p38 mitogen-activated protein kinase (p38 MAPK). Further, the changes in C33a and SiHa cells viability, migration and proliferation observed upon overexpression of gC1qR could be abrogated using the p38 MAPK inhibitor SB202190. Conclusion: These data indicate that gC1qR inhibits viability, migration and proliferation of cervical squamous cells carcinoma via the p38 MAPK signalling pathway.
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