scholarly journals Synthesis of Hybrid Fluoroquinolone-Boron Complexes and Their Evaluation in Cervical Cancer Cell Lines

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Hiram Hernández-López ◽  
Griselda Sánchez-Miranda ◽  
Jorge Gustavo Araujo-Huitrado ◽  
Angelica Judith Granados-López ◽  
Jesús Adrián López ◽  
...  

Quinolones are a family of antimicrobial agents that have been used in antibacterial and anticancer chemotherapy. Fluoroquinolone targets DNA gyrase and topoisomerase IV enzymes affecting several cellular processes, like cell death and proliferation; the best way to act is in the form of carboxylic acid or, recently, as quinolone-metal complex. In this work, the use of boron is shown as an alternative of metal to form a complex by incorporating to fluoroquinolone as an electron withdrawing substituent to activate the C-7 position chemoselectively for the production of new fluoroquinolone hybrids and test their effects on cell proliferation. Fluoroquinolone-boron complexes were synthesized according to the Gould–Jacobs cyclization method, and five hybrid fluoroquinolone-boron compounds were obtained by SNAr reaction, yielding 31 to 46%, at 80°C, and in 10 to 25 hours of reaction. The effect of the five fluoroquinolone-boron hybrids was evaluated in cervical cancer cell lines by cell proliferation assay. 7-hydantoin-fluoroquinolone-boron and 7-dihydropyridine-fluoroquinolone-boron complexes showed the strongest effect according to dose-response assay, respectively. The fluoroquinolone-boron hybrid complex showed proliferation inhibition in SiHa and CasKi cells, opening the possibility to use them as potential agents for the treatment of cancer.

2018 ◽  
Vol 96 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Yang Liu ◽  
Yanling Yang ◽  
Lei Li ◽  
Yuan Liu ◽  
Peng Geng ◽  
...  

Objective: This study investigated the effects of lncRNA SNHG1 on the proliferation, migration, and invasiveness of cervical cancer cells. Methods: Three pairs of cervical cancer tissue samples and their corresponding adjacent samples were analyzed using Human LncRNA Microarray V3.0 chip for differential analysis. The expression of SNHG1 in cervical cancer cell lines was verified by qRT–PCR. CCK8 assays and colony formation assays were used to study the changes in cell proliferation. Cell migration and Transwell assays were used to study changes in cell migration and invasiveness. Results: SNHG1 was highly expressed in cervical cancer tissues and cervical cancer cell lines. SNHG1 siRNA could knock-down the expression level of SNHG1 in cervical cancer cell lines HeLa and C33-A. After knock-down of SNHG1, cell proliferation and migration as well as invasiveness in HeLa and C-33A cells decreased. Conclusion: LncRNA SNHG1 promotes the development of cervical cancer cells.


2016 ◽  
Vol 242 (2) ◽  
pp. 184-193 ◽  
Author(s):  
Tawin Iempridee

Long non-coding RNA H19 is aberrantly expressed in multiple malignancies and its expression levels correlate with recurrence, metastasis, and patient survival. Despite numerous reports documenting the role of H19 in carcinogenesis, its contribution to cervical cancer development is still largely unknown. In this study, I observed that H19 expression was elevated in cervical cancer cell lines and could be detected in extracellular vesicles in the culture medium. In addition, I demonstrated, by overexpression and knockdown experiments, that H19 promoted cell proliferation and multicellular tumor spheroid formation without significantly affecting apoptosis and cell migration. Finally, treatment with transforming growth factor beta and hypoxia-mimetic CoCl2 could modulate H19 levels in a cell line-specific manner. These findings indicate that H19 promotes both anchorage-specific and -independent growth of cervical cancer cell lines and may serve as a potential target for cancer diagnosis and therapy.


2019 ◽  
Author(s):  
Siti Fairus Abdul Rahman ◽  
Kalaivani Muniandy ◽  
Yong Kit Soo ◽  
Elvin Yu Huai Tiew ◽  
Ke Xin Tan ◽  
...  

AbstractA combination of the BCL-2 inhibitors ABT-263 and A-1210477 inhibited cell proliferation in the HeLa, C33A, SiHa and CaSki human cervical cancer cell lines. Drug sensitivity was initially tested using 2-dimensional (2D) cell culture models. As ABT-263 binds to both BCL-2 and BCL-XL at high affinity, it was unclear whether the synergism of the drug combination was driven either by singly inhibiting BCL-2 or BCL-XL, or inhibition of both. Therefore, we used the BCL-2 selective inhibitor ABT-199 and the BCL-XL selective inhibitor A1331852 to resolved the individual antitumor activities of ABT-263 into BCL-2 and BCL-XL dependent mechanisms. A-1210477 was substituted with the orally bioavailable S63845. The SiHa, C33A and CaSki cell lines were resistant to single agent treatment of all three drugs, suggesting that none of these anti-apoptotic proteins singly mediate survival of the cells. HeLa cells were resistant to single agent treatment of ABT-199 and A1331852 but were sensitive to S63845 indicating that they depend on MCL-1 for survival. Co-inhibition of BCL-XL and MCL-1 with A1331852 and S63845 significantly inhibited cell proliferation of all four cell lines. Similar data were obtained with 3-dimensional spheroid cell culture models generated from two cervical cancer cell lines in vitro. Treatment with a combination of A1331852 and S63845 resulted in inhibition of growth and invasion of the 3D spheroids. Co-inhibition of BCL-2 and MCL-1 with ABT-199 and S63845, also inhibited cell proliferation of all cancer cell lines, except SiHa. However, the effect of the combination was not as pronounced as combination of A1331852 and S63845. Collectively, our data demonstrate that the combination of MCL-1-selective inhibitors with either selective inhibitors of either BCL-XL or BCL-2 may be potentially useful as treatment strategies for the management of cervical cancer.


2005 ◽  
Vol 97 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Todd D. Tillmanns ◽  
Scott A. Kamelle ◽  
Suresh Guruswamy ◽  
Natalie S. Gould ◽  
Teresa L. Rutledge ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1934 ◽  
Author(s):  
Eric Ehrke-Schulz ◽  
Sonja Heinemann ◽  
Lukas Schulte ◽  
Maren Schiwon ◽  
Anja Ehrhardt

Human papillomaviruses (HPV) cause malignant epithelial cancers including cervical carcinoma, non-melanoma skin and head and neck cancer. They drive tumor development through the expression of their oncoproteins E6 and E7. Designer nucleases were shown to be efficient to specifically destroy HPV16 and HPV18 oncogenes to induce cell cycle arrest and apoptosis. Here, we used high-capacity adenoviral vectors (HCAdVs) expressing the complete CRISPR/Cas9 machinery specific for HPV18-E6 or HPV16-E6. Cervical cancer cell lines SiHa and CaSki containing HPV16 and HeLa cells containing HPV18 genomes integrated into the cellular genome, as well as HPV-negative cancer cells were transduced with HPV-type-specific CRISPR-HCAdV. Upon adenoviral delivery, the expression of HPV-type-specific CRISPR/Cas9 resulted in decreased cell viability of HPV-positive cervical cancer cell lines, whereas HPV-negative cells were unaffected. Transduced cervical cancer cells showed increased apoptosis induction and decreased proliferation compared to untreated or HPV negative control cells. This suggests that HCAdV can serve as HPV-specific cancer gene therapeutic agents when armed with HPV-type-specific CRISPR/Cas9. Based on the versatility of the CRISPR/Cas9 system, we anticipate that our approach can contribute to personalized treatment options specific for the respective HPV type present in each individual tumor.


2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Benedict Shi Xiang Lian ◽  
Angeline En Hui Yek ◽  
Hemalata Shuvas ◽  
Siti Fairus Abdul Rahman ◽  
Kalaivani Muniandy ◽  
...  

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