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

Abstract

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.

Differential Interactome Based Drug Repositioning Unraveled Abacavir, Exemestane, Nortriptyline Hydrochloride, and Tolcapone as Potential Therapeutics for Colorectal Cancers

“…Carlini and coworkers ( Carlini et al, 2010 ) investigated the effect of abacavir in prostate cancer cell lines and observed that abacavir reduced cell growth, migration, and invasion processes. Another study investigated the effect of abacavir and its combination with other reverse transcriptase inhibitors in breast cancer cells and found an increase in apoptosis and a decrease in migration in treated cells ( Sekeroglu et al, 2021 ). On the other hand, Exemestane is already used in breast cancer, but Koutras and colleagues ( Koutras et al, 2009 ) observed the antiplatelet effect of Exemestane also in lung cancer cells.…”

Cerium oxide nanoparticles exert antitumor effects and enhance paclitaxel toxicity and activity against breast cancer cells

“…The MTT assay was performed as previously published 3,12 . Results were expressed as percent inhibition relative to control cells.…”

“…This resistance is an important problem for aggressive and poor prognosis cancers. Cancer cells can activate various mechanisms to evade the cytotoxicity of the drugs by altering or enhancing drug efflux, apoptotic pathways, or DNA repair mechanisms 2,3 . Eventually, the resistance of tumor cells to chemotherapy drugs leads to failure of treatment.…”

“…Although healthy (normal) cells activate protective and reparative mechanisms such as various free‐radical scavengers when exposed to radiation, they cannot block all the damage that ultimately leads to the death of normal tissue 4,5 . Therefore, more effective new compounds and treatments are required addressing the disadvantages of clinically available chemo/radio protectants, focusing on increasing the efficacy of chemotherapy and radiotherapy, obtaining better dose–response results, reducing toxic side effects, and improving efficacy and therapeutic index in cancer therapy 2,3,5 …”

Putative Repurposing of Lamivudine, a Nucleoside/Nucleotide Analogue and Antiretroviral to Improve the Outcome of Cancer and COVID-19 Patients

“…Also, Lamivudine has been shown to enhance the sensitivity of liver cancer cell lines to chemotherapy with sorafenib, by decreasing partially the expression of an apoptosis inhibitor (cIAP2), thus diminishing the viability of liver cancerous cells ( 46 ). Moreover, in cultured cancerous cell lines from human breast cancer it was also found that Lamivudine, combined with other ANNAs such as Abacavir, Stavudine, and Tenofovir, significantly increased apoptosis and decreased migration more effectively in the cancerous cell lines than in normal breast cell lines ( 47 ). This opens the possibility for further research to find the optimal combinations of ANNAs to decrease viability and migration of particular types of cancerous cells and tumors.…”