Amino acid transporter (xCT) influences the growth and progression of non-small cell lung cancer. So, a team of researchers used an anti-inflammatory drug known as sulfasalazine to reduce the formation of the tumor by inhibiting the function of xCT, reports a new study. The findings of the study are published in the journal Oncogene.
xCT is an amino acid transporter, which carries the amino acid cystine into the cells and exports glutamate, a chemical that nerve cells use to send signals to other cells. It provides the key building blocks for glutathione (GSH) synthesis, which feeds cancer cell function and growth. The researchers used sulfasalazine; an anti-inflammatory drug often used to treat Crohn's disease, rheumatoid arthritis, and related diseases, to reduce tumor formation by inhibiting the function of xCT.
‘Sulfasalazine is an anti-inflammatory drug which helps to reduce tumor formation in non-small cell lung cancer is also used to treat Crohn's disease, rheumatoid arthritis, and related diseases.’
Previous studies published in cancer research journals show sulfasalazine's ability to affect xCT in other forms of cancer, including breast, bladder and small cell lung cancer.
Researchers first examined xCT protein expression in non-small cell lung cancer cell lines and found larger quantities in the non-small cell lung cancer cells compared to normal lung tissue.
By analyzing protein expression of patients from Vanderbilt-Ingram Cancer Center, the researchers found patients with higher xCT expression have a lower five-year cancer survival rate. On the positive side, the data show xCT as a therapeutic targeting candidate.
Ji and Massion tested the cancer cells in the laboratory and mice, discovering that targeting xCT genetically or therapeutically could reduce the tumor formation in vitro (in cell culture) and in vivo (in living organisms). They also found only cells with elevated xCT expression were more sensitive to glutamine withdrawal. The results show strong evidence that lowering xCT may improve survival rates for individuals with non-small cell lung cancer.
"In conclusion, our results demonstrate that xCT is a major regulator of metabolic reprogramming with overarching effects on glucose metabolism, glutamine dependency, and intracellular GSH/GSSG redox balance. All these metabolic effects contribute to lung cancer development," Ji said.
The expression of xCT is correlated with a poor prognosis in non-small cell lung cancer and represents a new opportunity to therapeutically target this biomarker in molecularly stratified non-small cell lung cancer patients. Further studies are needed to better understand the unwanted communication between xCT and other tumor-associated cell signaling pathways such as MYC, KRAS, and NOTCH in the formation of lung cancer tumors.