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: 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.3 Biotech. 12/2013;
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ABSTRACT: Flavonoids have been intensively explored for their anti-cancer activity. In this study, a total synthetic flavonoid protoapigenone known as WYC02, was analysed for its potential anti-cancer activity on human cervical cancer cells as well as the underlying mechanisms for these effects. Using the site-moiety maps to explore the binding site similarity, pharmacophore and docking pose similarity. The effect of WYC02 on cell viability, migration, invasion, apoptosis as well as the underlying mechanisms were analysed in vitro using human cervical cancer cells. Effect of WYC02 on in vivo tumour growth was assessed in a tumour xenograft study. WYC02 inhibited cell proliferation, MMPs activity, migration and invasion in cervical cancer cells. We speculated that WYC02 might inhibit the activities of PIK3 family proteins including PIK3CA, PIK3CB, PIK3CD and PIK3CG. Indeed, WYC02 decreased the expression of PIK3 family proteins, especially PIK3CG, through ubiquitination and inhibited the activities of PIK3CG and PIK3 downstream molecules AKT1 and MTOR in cervical cancer cells. Furthermore, PIK3 signaling pathway was involved in the inhibitory effect of WYC02 on cervical cancer cell proliferation and tumour growth in vitro and in vivo. WYC02 inhibits cervical cancer cell proliferation and tumourigenesis via PIK3 signaling pathway and has the potential to be developed as a chemotherapeutic agent in cervical cancer.Basic & Clinical Pharmacology & Toxicology 02/2013; · 2.18 Impact Factor
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ABSTRACT: Introduction: Cervical cancer, the second most common gynecological malignant tumor seriously harmful to the health of women, remains a leading cause of cancer-related death for women in developing countries. Although a large amount of scientific research has been reported on plants as a natural source of treatment agents for cervical cancer, it is currently scattered across various publications. A systematic summary and knowledge of future prospects are necessary to facilitate further plant studies for anti-cervical cancer agents. Areas covered: This review generalizes and analyzes the current knowledge on the anti-cervical cancer properties and mechanisms involved for plants, and discusses the future prospects for the application of these plants. Expert opinion: This review mainly focuses on the plants which have been scientifically tested in vitro and/or in vivo and proved as potential agents for the treatment of cervical cancer. The failure of conventional chemotherapy to reduce mortality as well as serious side effects involved makes natural products ideal candidates for exerting synergism and attenuation effects on anticancer drugs. Although the chemical components and mechanisms of action of natural plants with anti-cervical cancer potential have been investigated, many others remain unknown. More investigations and clinical trials are necessary to make use of these medical plants reasonably.Expert Opinion on Investigational Drugs 06/2013; · 4.74 Impact Factor