Effects of Reverse Transcriptase Inhibitors on Proliferation, Apoptosis, and Migration in Breast Carcinoma Cells

2020 ◽  
pp. 109158182096149
Author(s):  
Zülal Atlı Şekeroğlu ◽  
Vedat Şekeroğlu ◽  
Nihan Küçük

High telomerase activity in human breast cancer is associated with aggressive tumors resulting in decreased survival. Recent studies have shown that telomerase inhibitors may display anticancer properties in some human cancer cell lines. In the present study, we examined the effects of 4 reverse transcriptase inhibitors (RTIs), used for the treatment of HIV; Abacavir (AC), Lamivudine (LV), Stavudine (SV), and Tenofovir (TF) on proliferation, apoptosis, and migration in the normal human mammary epithelial cell line, hTERT-HME1, and the human breast cancer cell line, MCF-7. Cells were treated with AC, LV, SV, or TF alone or in combination with paclitaxel (PAC), a known drug used to treat breast cancer. Conduct of the thiazolyl blue tetrazolium bromide assay demonstrated that AC, SV, and TF had stronger cytotoxic effects on MCF-7 cells than in hTERT-HME1 cells. The combined treatment of RTIs and PAC caused high rates of cell death in MCF-7 and low rates of cell death in HTERT-HME1 by apoptosis. The percentages of apoptotic cells in the treatment of AC and SV in combination with PAC for 48 and 72 hours were higher than PAC. Significantly increased apoptosis and decreased migration levels were found in MCF-7 cells treated with AC and co-treatment of AC+PAC or SV+PAC than HME1 cells. These treatments can also prevent migration capacity more than PAC. Therefore, a combination strategy based on telomerase inhibitors such as AC or SV and anticancer drugs may be more effective in the treatment of certain breast cancers.

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Thomas Klein ◽  
Jens Benders ◽  
Friederike Roth ◽  
Monika Baudler ◽  
Isabel Siegle ◽  
...  

Endogenously formed prostacyclin (PGI2) and synthetic PGI2analogues have recently been shown to regulate cell survival in various cell lines. To elucidate the significance of PGI2in human breast cancer, we performed immunohistochemistry to analyze expression of prostacyclin-synthase (PGIS) in 248 human breast cancer specimens obtained from surgical pathology files. We examined patients’ 10-year survival retrospectively by sending a questionnaire to their general practitioners and performed univariate analysis to determine whether PGIS expression correlated with patient survival. Lastly, the effects of PGI2and its analogues on cell death were examined in a human breast cancer cell line (MCF-7) and a human T-cell leukemia cell line (CCRF-CEM). PGIS expression was observed in tumor cells in 48.7% of samples and was associated with a statistically significant reduction in 10-year survival (P=0.038;n=193). Transient transfection of PGIS into MCF-7 cells exposed to sulindac increased cell viability by 50% and exposure to carbaprostacyclin protected against sulindac sulfone induced apoptosis in CCRF-CEM cells. Expression of PGIS is correlated with a reduced patient survival and protects against cell deathin vitro, suggesting that PGIS is a potential therapeutic target in breast cancer.


2002 ◽  
Vol 129 (1-2) ◽  
pp. 55-63 ◽  
Author(s):  
Christel M Olsen ◽  
Elise T.M Meussen-Elholm ◽  
Jørn A Holme ◽  
Jan K Hongslo

2021 ◽  
Vol 66 (1) ◽  
pp. 65-71
Author(s):  
Hung Nguyen Phi ◽  
Toan Tran Quoc ◽  
Tuan Nguyen Anh ◽  
Vy Trinh Ngoc Thao ◽  
Yen Ngo Thi Ngoc ◽  
...  

Three alkaloids (named rutaecarpine (1), evodiamine (2), schinifoline (3) and one phenylpropanoid, integrifoliodiol (4)) have been isolated from the EtOAc extract of the fruits of Tetradium ruticarpum (A. Juss.) T. G. Hartley collected in Lang Son province. Their structures have been identified by using 1D and 2D NMR spectroscopies. All four compounds were tested for their cytotoxicity against the human breast cancer cell line (MCF-7) and tamoxifen-resistant breast cancer cell line (MCF\TAMR). The results showed that rutaecarpine (1) inhibited the growth of MCF7 and MCF\TAMR with its IC50 values of 41.2 and 64.6 µM, respectively. In addition, compounds 1, 2, and 4 showed moderate activity toward MCF-7 cell line.


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