scholarly journals Baicalein inhibits the invasion of human cervical cancer cells by inhibiting the hedgehog/Gli signaling pathway

2020 ◽  
Vol 19 (1) ◽  
pp. 115-120
Author(s):  
Hai Yang ◽  
Jiyi Xia ◽  
Yan Li ◽  
Yong Cao ◽  
Li Tang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Hela Cells ◽  
Colony Formation ◽  
Diphenyltetrazolium Bromide ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer Cells ◽  
Human Cervical Cancer

Purpose: To identify the role of baicalein in human cervical cancer and to determine whether baicalein treatment affects hedgehog/Gli signaling pathway. Methods: Cell proliferation was evaluated by MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and colony formation assays. Cell death rate was assessed by PI-staining and FACS assay. Furthermore, cell invasion was assessed by Transwell assay while the levels of the key proteins were measured by western blotting analysis. Results: Baicalein suppressed the viability and proliferation of HeLa cells. The colony formation ability and relative migration rate were significantly decreased in the HeLa cells treated with 50 μM baicalein. Furthermore, the levels of Shh, Gli1, MMP-9, and VEGF declined significantly in baicalein-treated cells. Conclusion: The results demonstrate that baicalein inhibits the growth and invasiveness of cervical cancer cells partly by suppressing the activation of hedgehog/Gli signaling pathway in a concentrationdependent manner. Keywords: Cervical cancer, baicalein, hedgehog/Gli pathway, MMP-9

Amiodarone’s major metabolite, desethylamiodarone, induces apoptosis in human cervical cancer cells

2018 ◽  
Vol 96 (10) ◽  
pp. 1004-1011 ◽  
Author(s):  
Zita Bognar ◽  
Katalin Fekete ◽  
Rita Bognar ◽  
Aliz Szabo ◽  
Reka A. Vass ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Hela Cell ◽  
Cancer Cells ◽  
Hela Cells ◽  
Dead Cell ◽  
Dependent Manner ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer Cells ◽  
Human Cervical Cancer

Previously, we found that desethylamiodarone (DEA) may have therapeutic potentiality in bladder cancer. In this study, we determined its effects on human cervical cancer cells (HeLa). Cell viability was evaluated by Muse Cell Count & Viability Assay; cell apoptosis was detected by Muse Annexin V & Dead Cell Assay. Cell cycle was flow cytometrically determined by Muse Cell Cycle Kit and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33342 staining. The changes in the expression levels of apoptosis-related proteins in the HeLa cells were assessed by immunoblot. Our results showed that DEA significantly inhibited the proliferation and viability of HeLa cells and induced apoptosis in vitro in dose-dependent and also in cell cycle-dependent manner because DEA induced G0/G1 phase arrest in the HeLa cell line. We found that DEA treatment downregulated the expression of phospho-Akt and phospho-Bad. In addition, DEA could downregulate expression of Bcl-2, upregulate Bax, and induce cytochrome c release. Our results indicate that DEA might have significance as an anti-tumor agent against human cervical cancer.

scholarly journals Hsp90 Inhibitor SNX-2112 Enhances TRAIL-Induced Apoptosis of Human Cervical Cancer Cells via the ROS-Mediated JNK-p53-Autophagy-DR5 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-26
Author(s):  
Liubing Hu ◽  
Yan Wang ◽  
Zui Chen ◽  
Liangshun Fu ◽  
Sheng Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Hela Cells ◽  
Cell Apoptosis ◽  
Hsp90 Inhibitor ◽  
Cervical Cancer Cells ◽  
Ros Scavenger ◽  
Induced Apoptosis ◽  
Human Cervical Cancer

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell apoptosis-inducing factor that can induce apoptosis in a variety of cancer cells. However, resistance to TRAIL in cancer cells is a huge obstacle in creating effective TRAIL-targeted clinical therapies. Thus, agents that can either enhance the effect of TRAIL or overcome its resistance are needed. In this study, we combined TRAIL with SNX-2112, an Hsp90 inhibitor we previously developed, to explore the effect and mechanism that SNX-2112 enhanced TRAIL-induced apoptosis in cervical cancer cells. Our results showed that SNX-2112 markedly enhanced TRAIL-induced cytotoxicity in HeLa cells, and this combination was found to be synergistic. Additionally, we found that SNX-2112 sensitized TRAIL-mediated apoptosis caspase-dependently in TRAIL-resistant HeLa cells. Mechanismly, SNX-2112 downregulated antiapoptosis proteins, including Bcl-2, Bcl-XL, and FLIP, promoted the accumulation of reactive oxygen species (ROS), and increased the expression levels of p-JNK and p53. ROS scavenger NAC rescued SNX-2112/TRAIL-induced apoptosis and suppressed SNX-2112-induced p-JNK and p53. Moreover, SNX-2112 induced the upregulation of death-receptor DR5 in HeLa cells. The silencing of DR5 by siRNA significantly decreased cell apoptosis by the combined effect of SNX-2112 and TRAIL. In addition, SNX-2112 inhibited the Akt/mTOR signaling pathway and induced autophagy in HeLa cells. The blockage of autophagy by bafilomycin A1 or Atg7 siRNA abolished SNX-2112-induced upregulation of DR5. Meanwhile, ROS scavenger NAC, JNK inhibitor SP600125, and p53 inhibitor PFTα were used to verify that autophagy-mediated upregulation of DR5 was regulated by the SNX-2112-stimulated activation of the ROS-JNK-p53 signaling pathway. Thus, the combination of SNX-2112 and TRAIL may provide a novel strategy for the treatment of human cervical cancer by overcoming cellular mechanisms of apoptosis resistance.

scholarly journals Furan-Conjugated Tripeptides as Potent Antitumor Drugs

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1684
Author(s):  
Hunain Ali ◽  
Almas Jabeen ◽  
Rukesh Maharjan ◽  
Muhammad Nadeem-ul-Haque ◽  
Husena Aamra ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Hela Cells ◽  
Umbilical Vein ◽  
Human Fibroblasts ◽  
Cervical Cancer Cells ◽  
Umbilical Vein Endothelial Cells ◽  
Relationship Of ◽  
Human Cervical Cancer Cells ◽  
Human Cervical Cancer

Cervical cancer is among the leading causes of death in women. Chemotherapy options available for cervical cancer include highly cytotoxic drugs such as taxol, cisplatin, 5-florouracil, and doxorubicin, which are not specific. In the current study, we have identified a new peptide conjugate (Fur4-2-Nal3-Ala2-Phe1-CONH2) (conjugate 4), from screening of a small library of tripeptide-conjugates of furan, as highly potent anticancer compound against human cervical cancer cells (HeLa cells) (IC50 = 0.15 ± 0.05 µg/mL or 0.28 +/− 0.09 µM). Peptides were constructed on Rink amide resin from C- to N-terminus followed by capping by α-furoic acid moiety. The synthesized peptides were purified by recycling RP-HPLC, and structures of all the peptides were confirmed by using FABMS/ESIMS, 1H- NMR, 13C-NMR, and HR-FABMS. Conjugate 4 was furthermore found to be specifically active against human cervical cancer cells since it did not inhibit the proliferation of other human normal cells (HUVEC (human umbilical vein endothelial cells) and IMR-90 (normal human fibroblasts)), and cancer cells tested (HUVEC, MCF-7, and MDA-MB-231 cells), as well as in mice 3T3 cells (normal fibroblasts). This study revealed a good structure activity relationship of various peptide conjugates. Conjugate 4 in branched forms (4a and 4b) were also synthesized and evaluated against HeLa cells, and results revealed that both were inactive. Atomic force microscopy (AFM) studies and staining with rhodamine 123 and propidium iodide (PI) revealed that conjugate 4 possesses a membranolytic effect and causes the loss of mitochondrial membrane potential.

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