BACKGROUND : Tumourigenic cells modify metabolic pathways in order to facilitate increased proliferation and cell survival
resulting in glucose- and glutamine addiction. Previous research indicated that glutamine deprivation resulted
in potential differential activity targeting tumourigenic cells more prominently. This is ascribed to tumourigenic cells
utilising increased glutamine quantities for enhanced glycolysis- and glutaminolysis. In this study, the effects exerted
by glutamine deprivation on reactive oxygen species (ROS) production, mitochondrial membrane potential, cell proliferation
and cell death in breast tumourigenic cell lines (MCF-7, MDA-MB-231, BT-20) and a non-tumourigenic breast
cell line (MCF-10A) were investigated.
RESULTS : Spectrophotometry demonstrated that glutamine deprivation resulted in decreased cell growth in a timedependent
manner. MCF-7 cell growth was decreased to 61% after 96 h of glutamine deprivation; MDA-MB-231 cell
growth was decreased to 78% cell growth after 96 h of glutamine deprivation, MCF-10A cell growth was decreased
89% after 96 h of glutamine deprivation and BT-20 cell growth decreased to 86% after 24 h of glutamine deprivation
and remained unchanged until 96 h of glutamine deprivation. Glutamine deprivation resulted in oxidative stress
where superoxide levels were significantly elevated after 96 h in the MCF-7- and MDA-MB-231 cell lines. Timedependent
production of hydrogen peroxide was accompanied by aberrant mitochondrial membrane potential.
The effects of ROS and mitochondrial membrane potential were more prominently observed in the MCF-7 cell line
when compared to the MDA-MB-231-, MCF-10A- and BT-20 cell lines. Cell cycle progression revealed that glutamine
deprivation resulted in a significant increase in the S-phase after 72 h of glutamine deprivation in the MCF-7 cell line.
Apoptosis induction resulted in a decrease in viable cells in all cell lines following glutamine deprivation. In the MCF-7
cells, 87.61% of viable cells were present after 24 h of glutamine deprivation.
CONCLUSION : This study demonstrates that glutamine deprivation resulted in decreased cell proliferation, timedependent-
and cell line-dependent ROS generation, aberrant mitochondrial membrane potential and disrupted
cell cycle progression. In addition, the estrogen receptor positive MCF-7 cell line was more prominently affected. This study contributes to knowledge regarding the sensitivity of breast cancer cells and non-tumorigenic cells to glutamine
Additional file 1. Table of mitotic indices, table of cell cycle progression
and table of Annexin V/PI staining.