scholarly journals A Novel Signature of CCNF-Associated E3 Ligases Collaborate and Counter Each Other in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2873
Author(s):  
Shu-Chun Chang ◽  
Chin-Sheng Hung ◽  
Bo-Xiang Zhang ◽  
Tsung-Han Hsieh ◽  
Wayne Hsu ◽  
...  

Breast cancer (BRCA) malignancy causes major fatalities amongst women worldwide. SCF (Skp1-cullin-F-box proteins) E3 ubiquitin ligases are the most well-known members of the ubiquitination–proteasome system (UPS), which promotes cancer initiation and progression. Recently, we demonstrated that FBXL8, a novel F-box protein (SCFF-boxes) of SCF E3 ligase, accelerates BRCA advancement and metastasis. Since SCFF-boxes is a key component of E3 ligases, we hypothesized that other SCFF-boxes besides FBXL8 probably collaborate in regulating breast carcinogenesis. In this study, we retrospectively profiled the transcriptome of BRCA tissues and found a notable upregulation of four SCFF-box E3 ligases (FBXL8, FBXO43, FBXO15, and CCNF) in the carcinoma tissues. Similar to FBXL8, the knockdown of FBXO43 reduced cancer cell viability and proliferation, suggesting its pro-tumorigenic role. The overexpression of CCNF inhibited cancer cell progression, indicating its anti-tumorigenic role. Unexpectedly, CCNF protein was markedly downregulated in BRCA tissues, although its mRNA level was high. We showed that both E3 ligases, FBXL8 and FZR1, pulled down CCNF. Double knockdown of FBXL8 and FZR1 caused CCNF accumulation. On the other hand, CCNF itself pulled down a tumorigenic factor, RRM2, and CCNF overexpression reduced RRM2. Altogether, we propose a signature network of E3 ligases that collaboratively modulates CCNF anti-cancer activity. There is potential to target BRCA through modulation of the partnership axes of (i) CCNF-FBXL8, (ii) CCNF-FZR1, and (iii) CCNF-RRM2, particularly, via CCNF overexpression and activation and FBXL8/FZR1 suppression.

Oncotarget ◽  
2017 ◽  
Vol 8 (60) ◽  
pp. 101461-101474 ◽  
Author(s):  
Yung-Lung Chang ◽  
Yu-Juei Hsu ◽  
Ying Chen ◽  
Yi-Wen Wang ◽  
Shih-Ming Huang

2013 ◽  
Vol 850-851 ◽  
pp. 1291-1294
Author(s):  
Xiu Rui Han ◽  
Xian Chao Li ◽  
Hong Zong Si ◽  
Cui Zhu Ge ◽  
Hua Gao ◽  
...  

Using the GEP,the QSAR model for anti-cancer activity of 38 compounds in 5 cancer cell lines was establish. These compounds are a novel class of anticarcinogen named tricyclic 5:7:5-fused diimidazo [4, 5-d:4, 5-f ][1, diazepines. The carcinoma cell lines involved in this research are A549 lung cancer, MCF-7 breast cancer, MDA-MB-231 breast cancer, OVCAR-3 ovarian cancer and PC-3 prostate cancer. Accuracies of these models in training group and test group are over 90%, showing perfect predictive ability. This QSAR model will be great valuable in providing guidance for future designing and synthesizing of anticancer drugs.


2015 ◽  
Vol 37 (7) ◽  
pp. 1355-1359 ◽  
Author(s):  
Shahedeh Shahbazian ◽  
Azim Akbarzadeh ◽  
Sepideh Torabi ◽  
Mansour Omidi

Author(s):  
Tati Herlina ◽  
Unang Supratman ◽  
Anas Subarnas ◽  
Supriyatna Sutardjo ◽  
Suseno Amien ◽  
...  

Erythrina plants, locally known as “dadap ayam”, are higher plant species and have been used as a folk medicine for treatment of cancer. To prove the effectiveness of the leaves and stem bark of E. variegata as an anti-cancer agent, the assay in this research was focused on in vitro test towards breast cancer cell T47D. In the course of our continuing search for novel anti-cancer agent from Erythrina plants, the methanol extract of the leaves and stem bark of E. variegata showed significant anti-cancer activity against breast cancer cell T47D in vitro using the Sulphorhodamine B (SRB) assay. By using the anti-cancer activity to follow the separations, the methanol extract was separated by combination of column chromatography. The chemical structure of an anti-cancer compounds were determined on the basis of spectroscopic evidence and comparison with the previously reported and identified as an erythrina alkaloid (1) and isoflavonoid (2). Compounds (1-2) showed anti-cancer activity against breast cancer cell T47D used with IC50 of  1.0 and 3.3 µg/mL, respectively. This results strongly suggested that E. variegata is promising sources for anti-cancer agents. Keywords: Anti-cancer, Erythrina variegata, Leguminoseae


Author(s):  
Jinsha Koroth ◽  
Snehal Nirgude ◽  
Shweta Tiwari ◽  
Vidya Gopalakrishnan ◽  
Raghunandan Mahadeva ◽  
...  

Abstract Background Curcumin is known for its multitude of medicinal properties, including anti-cancer and migrastatic activity. Efforts to overcome poor bioavailability, stability, and side effects associated with the higher dose of curcumin has led to the development of newer derivatives of curcumin. Thus, the focus of this study is to screen novel curcumin derivatives, namely ST03 and ST08, which have not been reported before, for their cytotoxicity and migrastatic property on cancer cells. Methods Anti-cancer activity of ST03 and ST08 was carried out using standard cytotoxicity assays viz., LDH, MTT, and Trypan blue on both solid and liquid cancer types. Flow cytometric assays and western blotting was used to investigate the cell death mechanisms. Transwell migration assay was carried out to check for migrastatic properties of the compounds. Results Both the compounds, ST03 and ST08, showed ~ 100 fold higher potency on liquid and solid tumour cell lines compared to its parent compound curcumin. They induced cytotoxicity by activating the intrinsic pathway of apoptosis in the breast (MDA-MB-231) and ovarian cancer cell lines (PA-1) bearing metastatic and stem cell properties, respectively. Moreover, ST08 also showed inhibition on breast cancer cell migration by inhibiting MMP1 (matrix metalloproteinase 1). Conclusion Both ST03 and ST08 exhibit anti-cancer activity at nanomolar concentration. They induce cell death by activating the intrinsic pathway of apoptosis. Also, they inhibit migration of the cancer cells by inhibiting MMP1 in breast cancer cells.


2021 ◽  
Vol 5 (2) ◽  
pp. 263-273
Author(s):  
Kehinde S. Salako

Background: Cancer is one of the foremost contributors to global disease bur den and constantly requires new therapeutic options. The development of new drugs has failed to keep up with its incidence. Hence, drug reprofiling strategies are emerging as novel therapeutic options. The study aimed to evaluate the anti-cancer activity of amodiaquine (anti-malarial drug) using a combination of murine and human breast cancer cell lines Methods: Amodiaquine was authenticated by ultra-violet spectrophotometry, high- performance liquid chromatography and 1D nuclear magnetic resonance. In vitro cytotoxicity of amodiaquine was evaluated against three breast cancer cell lines. MDA-MB-453, 4T1 and MDA-MB-231 cells were incubated with the drug at different concentrations (0.78, 1.56, 3.13, 6.25, 12.50, 25.00, 50.00, 100.00 μM) for 72 h, after which cell viability testing was conducted using the cell counting kit-8 assay. Negative control in which no drug was added to the cells was also evaluated. The flow cytometry analysis of MDA-MB-231 cells when treated with amodiaquine was also evaluated by a flow cytometer using annexin V/propidium iodide staining assay. Results: Cell viability studies showed that the IC50 values of amodiaquine on MDA-MB-453, 4T1, and MDAMB-231 cells were 6.48 ± 1.12, 10.50 ± 1.17, and 19.23 ± 1.16 μM, respectively. The flow cytometry analysis of MDA-MB-231 cancer cells treated with amodiaquine showed cancer cell death by necrosis. Conclusion: This study has shown that amodiaquine may be potentially reprofiled as an anti-cancer agent in managing androgen receptor-positive / HER-2 positive and triple-negative breast cancer types. An additional probable mechanism of action of anti-cancer activity of amodiaquine was found to be necrosis .


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