Reduction of Rapid Proliferating Tumour Cell Lines by Inhibition of the Specific Glycine Transporter GLYT1

Abstract

Studies have highlighted the relevance of extracellular glycine and serine in supporting high growth rates of rapidly proliferating tumours. The present study analysed the role of the specific glycine transporter GLYT1 in supplying glycine to cancer cells and maintaining cell proliferation. GLYT1 knockdown in the rapidly proliferating tumour cell lines A549 and HT29 reduced the number of viable cells by approximately 30% and the replication rate presented a decrease of about 50% when compared to cells transfected with control siRNA. In contrast, when compared to control, GLYT1 siRNA had only a minimal effect on cell number of the slowly proliferating tumour cell line A498, reducing the number of viable cells by 7% and no significant difference was observed when analysing the replication rate between GLYT1 knockdown and control group. When utilising a specific GLYT1 inhibitor, ALX-5407, the doubling time of rapidly proliferating cells increased by about 8 h presenting a significant reduction in the number of viable cells after 96 h treatment when compared to untreated cells. Therefore, these results suggest that GLYT1 is required to maintain high proliferation rates in rapidly proliferating cancer cells and encourage further investigation of GLYT1 as a possible target in a novel therapeutic approach.

Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production

“…Glycine deficiency decreases the synthesis of GSH and promotes the production of ROS. Glycine can be transported into cells via the specific glycine transporters GLYT1 and GLYT2, as well as by a variety of non-specific amino acid transporters: SLC6A14, SLC36A1, SLC36A1, SLC38A2 and SLC38A4 [132]. Recently, SLC6A14 and SLC38A5 have been shown to be upregulated in various cancers and mediate the influx of glutamine, serine, glycine and methionine into cancer cells and are suitable for the rapid proliferation of cancer cells [133].…”

Berberine Inhibited Growth and Migration of Human Colon Cancer Cell Lines by Increasing Phosphatase and Tensin and Inhibiting Aquaporins 1, 3 and 5 Expressions

“…The colorectal cancer cell lines (HT-29, SW-480 and HCT-116) were cultured in T25 culture flasks at seeding density of 1 × 10 6 /flask. Cells were allowed to grow at 37 • C, 5% CO 2 and 95% relative humidity to a confluence of 80-85% and then exposed to three different concentrations of berberine (10, 30 and 100 µM) and incubated for 24, 48 and 72 h. [26] Total RNA was extracted using SV Total RNA Isolation System kit (Promega, Minneapolis, MN 55413, USA) [27]. The first strand of cDNA was synthesized using Go-ScriptTM Reverse Transcriptase System (Promega, USA) [28].…”

Cancer Metabolism and Resistance to Cell Death: Novel Therapeutic Perspectives

“…Bierhals and colleagues showed that glycine uptake through the transporter GLYT1 is necessary to sustain the proliferation of colorectal and non-small-cell carcinoma rapidly proliferating cells [ 8 ]. Interestingly, glycine can be incorporated directly and indirectly (through one-carbon metabolism and the trans-sulphuration pathway) into glutathione, thus contributing to ROS scavenging.…”