Propranolol Inhibits the Growth of Cervical Cancer Cells by Inhibiting Cyclic Guanosine Monophosphate/Protein Kinase G (cGMP/PKG) Pathway

This study assesses the therapeutic effect of propranolol on cervical cancer and its mechanism. Propranolol’s effect on cervical cancer was evaluated by MTT, Western blotting, flow cytometry and colony formation. By searching Drug Bank and String, cGMP/PKG signaling might be downstream targets of propranolol for subsequent analysis. Our results found that propranolol could significantly inhibit Hela and SiHA cell vitality and clone formation in a dose dependent manner. Further, Annexin V-PE/7-AAD Apoptosis Detection assay showed that propranolol could increase Hela and SiHA cell apoptosis. Finally, propranolol attenuated the phosphorylation level of VASP at Ser239 which is critical for PKG activation. In conclusion, propranolol suppressed cervical cancer cell proliferation via inhibition of cGMP/PKG signaling, which provides an affordable and effective method for cervical cancer remedy.

Antitumor activity of gambogic acid lysinate in human SiHa cells in vitro and in vivo

Background: Cervical cancer is a major cause of death for women worldwide and human papillomavirus (HPV) infection is the main cause of cervical cancer. The purpose of this study was to explore the anti-tumor activity of gambogic acid lysinate and clarify its mechanism in SiHa cells. Methods: In the present study, cell viability was detected by means of an MTT assay, a cell growth curve was drawn with Microsoft Excel 2010, the cell cycle and cell apoptosis were evaluated by flow cytometry, Western blotting was employed to explore the mechanism of gambogic acid lysinate, and caspase-3 activity was determined with a colorimetric Caspase-3 assay kit. Additionally, the in vivo antitumor activity of gambogic acid lysinate was studied through a xenograft tumor model established with nude mice. Results: The results showed that gambogic acid lysinate inhibited the proliferation of both SiHa cells (half-maximal inhibitory concentration (IC50) values: 0.83 μmol/l and 0.77 μmol/l for 48 h and 72 h) and HeLa cells (IC50 >2 μmol/l). In SiHa cells, gambogic acid lysinate (1 and 2 μmol/l) inhibited cell proliferation and 2 μmol/l gambogic acid lysinate induced cell apoptosis and decreased the number of S phase cells. Both 1 and 2 μmol/l gambogic acid lysinate increased the number of G0/G1 phase cells. The results of a Western blot assay demonstrated that P53 and P21 were involved in SiHa cell G0/G1 phase arrest and that Bcl-2 and BAX were involved in SiHa cell apoptosis. An in vivo study showed that the growth of SiHa cell xenograft tumors was inhibited by gambogic acid lysinate (2.5 mg/kg body weight), however, gambogic acid lysinate (2.5 mg/kg body weight) had no significant effect on mouse weight gain. Conclusions: gambogic acid lysinate is a promising candidate for cervical cancer therapy.

Phenolic Compounds from Polygonum chinense Induce Growth Inhibition and Apoptosis of Cervical Cancer SiHa Cells

Cervical cancer is considered to be one of the most serious malignant tumors in women. Natural compounds have been considered as important sources in the search for new anticancer agents. Polygonum chinense (PC) has been used as herbal medicine and Chinese cool tea. By activity-guided of the extracts from PC, PCwater shows good growth inhibition on SiHa cell, then by chromatographic analysis (HPLC and HPLC-MS/MS), we found twelve components, seven were phenolic compounds (PHE), two PHE named ellagic acid and corilagin were found to show strong growth inhibition effects in SiHa cell dose-dependently, while the seven phenolic compounds showed low inhibition on the common human HcerEpic cell. Further research found ellagic acid and corilagin induced G2 phase cell cycle arrest by upregulating levels of P53, Bcl-2, caspase 3, and caspase 9, while the Bax was reduced. These results suggested that PHE from PC might have potential anticancer effects against SiHa cells by acting through the apoptosis pathway, PHE from PC might have the potential to be used as a nutraceutical for the prevention and treatment of ovarian cancer.

Microarray screening of differentially expressed genes after up-regulating miR-205 or down-regulating miR-141 in cervical cancer cells

Cervical cancer is one of the most common gynecological malignancies. However,studies on the expression and molecular mechanism of miR-205 and miR-141 in CC are insufficient recently. Expression profile microarray with 21329 Oligo DNA were used to detect the expression of mRNAs in miR-205 up-regulated or miR-141 down-regulated HeLa and SiHa cells and mRNAs in normal HeLa and SiHa cells. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to assess the potential pathways of miR-205 in SiHa cell.Compared with normal HeLa cell, there were 38 differentially expressed genes (DEGs) in miR-205 up-regulated HeLa cell. Nine were up-regulation genes and 29 were down-regulation genes. There were 23 DEGs in miR-141 down-regulated HeLa cell. One was up-regulated and 22 were down-regulated. Compared with normal SiHa cell, there were 128 DEGs in miR-205 up-regulated SiHa cell. One hundred and three were up-regulation genes and 25 were down-regulation genes. There were 80 DEGs in miR-141 down-regulated SiHa cell. Forty two were up-regulation genes and 28 were down-regulation genes. For miR-205 up-regulated SiHa cell, GO outcome showed that “ubiquitin-protein ligase activity”, “MAP kinase phosphatase activity”, were the most enriched terms (P < 0.05). And in KEGG analysis, “Cell cycle” was notably enriched, and Smad4 in this pathway was up-regulated (P < 0.05). Expression profile microarray technology can effectively screen out DEGs in cervical cancer cells after up-regulating miR-205 or down-regulating miR-141. Which may enable us to understand the pathogenesis and lay an important foundation for the prevention and treatment of cervical cancer.

Anticancer Potential of Fruit Extracts from Vatica diospyroides Symington Type SS and Their Effect on Program Cell Death of Cervical Cancer Cell Lines

Vatica diospyroides Symington is locally known as Chan-Ka-Pho in Thailand. Ancient people have used it as therapeutic plant for cardiac and blood tonic cure. The purpose of this study was to investigate the potential cytotoxicity and selectivity of the extracts from V. diospyroides type SS fruit on cervical cancer HeLa and SiHa cell lines and to examine its underlying mechanism of action. MTT assay revealed that the extracts showed inhibition of cell survival in a dose-dependent manner and exhibited highly cytotoxic activity against both HeLa and SiHa cells with IC50 value less than 20 μg/mL along with less toxicity against L929 cells. Acetone cotyledon extract (ACE) showed the best selectivity index value of 4.47 (HeLa) and 3.51 (SiHa). Distinctive morphological changes were observed in ACE-treated cervical cancer cells contributing to apoptosis action. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that ACE induced apoptosis in HeLa and SiHa cell lines in a dose-dependent manner. Treatment of ACE with half IC50 caused DNA fragmentation and also activated increasing of bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure. The results suggest that ACE has potent and selective cytotoxic effect against cervical cancer cells and the potential to induce bax and caspase-8-dependent apoptosis. Hence, the ACE could be further exploited as a potential lead in cancer treatment.