The Effect of combined treatment of Telomerase increasing Compounds and chemotherapy on Breast Cancer Stem Cells

Cancer stem cells (CSCs) are a subpopulation of cancer cells in some tumors, that possess characteristics associated with normal stem cells, such as self-renewal and proliferation. These properties contribute to tumor development and metastasis. Most of the time, CSCs are in quiescent state, which contributes to resistance to stress and chemotherapy.

CSCs are able to grow as sphere-like structures, termed “mammospheres”, which enables their isolation and expansion in culture.

Telomerase is active in tumor cells and not in normal somatic cells and its canonical activity is the re-elongation of telomeres and thus enabling cell growth and proliferation.

We hypothesized that increasing telomerase expression by activator compounds may result in CSCs leaving the quiescent state and contribute to proliferation that will result in cells becoming sensitive to chemotherapy.

In this study, we investigated the effect of the telomerase activating compounds AGS, developed in our laboratory, on the amount and proliferation rate of the spheres and the efficacy of combined treatment of AGS and chemotherapy on CSC`s isolated from MCF7 human breast cancer cell line.

Following AGS treatment, we observed a decrease in the rate of mammosphere cell proliferation. In addition, combined treatment of AGS and chemotherapy is more effective compared to the chemotherapy alone.

These data suggest that affecting telomerase expression in breast CSCs under certain conditions increased their sensitivity to some of the anti-cancer drugs. Although the exact biochemical mechanism is unclear, our data suggest a possible new therapeutic strategy for the eradication of breast CSCs.