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.
"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). "
[Show abstract][Hide abstract] ABSTRACT: Cancer is a major public health concern in both developed and developing countries. Several plant-derived anti-cancer agents including taxol, vinblastine, vincristine, the campothecin derivatives, topotecan, irinotecan and etoposide are in clinical use all over the world. Other promising anti-cancer agents include flavopiridol, roscovitine, combretastatin A-4, betulinic acid and silvestrol. From this list one can well imagine the predominance of polyphenols, flavonoids and their synthetic analogs in the treatment of ovarian, breast, cervical, pancreatic and prostate cancer. Flavonoids present in human diet comprise many polyphenolic secondary metabolites with broad-spectrum pharmacological activities including their potential role as anti-cancer agents. A positive correlation between flavonoids-rich diet (from vegetables and fruits) and lower risk of colon, prostate and breast cancers lead to a question that whether flavonoids mediate the protective effects as chemopreventive agents or can interact with different genes and proteins to play role in chemotherapy. The current review emphasizes onto the therapeutic potential of flavonoids and their synthetic analogs as anti-cancer agents by providing new insights into the factors, regulation and molecular mechanisms along with their significant protein interactions.
"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). "
[Show abstract][Hide abstract] 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. DOI:10.3892/etm.2012.771 · 1.27 Impact Factor
[Show abstract][Hide abstract] 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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