Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach

Abstract

Glutamine metabolism has been proved to be dysregulated in many cancer cells, and is essential for proliferation of most cancer cells, which makes glutamine an appealing target for cancer therapy. In order to be well used by cells, glutamine must be transported to cells by specific transporters and converted to glutamate by glutaminase. There are currently several drugs that target glutaminase under development or clinical trials. Also, glutamine metabolism restriction has been proved to be effective in inhibiting tumor growth both in vivo and vitro through inducing apoptosis, growth arrest and/or autophagy. Here, we review recent researches about glutamine metabolism in cancer, and cell death induced by targeting glutamine, and their potential roles in cancer therapy.

From Krebs to clinic: glutamine metabolism to cancer therapy

“…A few combinations are notable because they reveal novel consequences of glutamine metabolism. Specific inhibition of the anti-apoptotic protein BCL-2 synergizes with glutaminase inhibition 53 , consistent with the described role of glutamine in controlling expression and activity of pro- and anti-apoptotic proteins, as reviewed recently 180 . Similarly, the synergism between glutamine withdrawal and chemical activation of the ISR with the retinoid-derivative fenretinide 65 shows that glutamine can suppress this stress response through various mechanisms, as discussed above.…”

Erratum: From Krebs to clinic: glutamine metabolism to cancer therapy

“…A few combinations are notable because they reveal novel consequences of glutamine metabolism. Specific inhibition of the anti-apoptotic protein BCL-2 synergizes with glutaminase inhibition 53 , consistent with the described role of glutamine in controlling expression and activity of pro-and anti-apoptotic proteins, as reviewed recently 180 . Similarly, the synergism between glutamine withdrawal and chemical activation of the ISR with the retinoid-derivative fenretinide 65 shows that glutamine can suppress this stress response through various mechanisms, as discussed above.…”

Plasma-free amino acid profiles are predictors of cancer and diabetes development

“…Among all of the amino acids, Gln has attracted great attentions as cancer cells are known to be avid consumers of Gln. 50, 51 Building on the Warburg effect, 52 cancer cells extensively use Gln to produce ATP (adenosine-triphosphate) to sustain anabolism, which is necessary for tumor growth and proliferation. It has been demonstrated that breast cancer cell lines expressing high levels of c- MYC were dependent on Gln for their survival and growth.…”