Exercise as a Kynurenine Pathway Modulator in Cancer: Traditional Review

Abstract

The overactivation of related enzymes of the kynurenine pathway in cancer and increase of chemical conversion metabolites in blood serum levels provide an immunologically sensitive microenvironment for mutant cells to survive and invade surrounding tissues. In particular, overactivation of indoleamine 2,3-dioxygenase 1 is thought to play a role as a determinant of the pathogenesis and poor disease prognosis in various cancers such as gastrointestinal cancers, gynecological cancers, hematological malignancies, breast cancer, lung cancer, glioma, melanoma, prostate, and pancreatic cancer. Additionally, kynurenic acid has been shown to increase quinolinic acid concentrations in the cerebrospinal fluid, leading to inflammation and leading to depressive symptoms. In this context, research on kynurenine pathway metabolites has gained momentum in explaining tumor formation, prognosis, and side effects due to cancer itself or its treatments. Previous studies have shown that both acute and chronic exercise can cause up/down-regulation of kynurenine pathway enzymes and metabolites in various diseases (such as diabetes, depression, and multiple sclerosis). The number of studies investigating the effectiveness of exercise as a mediator of the kynurenine pathway in the field of cancer is very limited. In this traditional review, current knowledge of exercise-induced modulations of the kynurenine pathway, the underlying mechanisms, as well as the relationship between exercise-induced kynurenine pathway and exercise/ cancer will be examined.

Keywords

• Kynurenine
• tryptophan
• cancer
• exercise

Kanserde Kinürenin Yolağı Modülatörü Olarak Egzersiz: Geleneksel Derleme

Abstract

Kanserde kinürenin yolağının ilgili enzimlerinin aşırı aktivasyonu ve kimyasal dönüşüm metabolitlerinin kan serum seviyelerindeki artışı, mutant hücrelerin hayatta kalması ve çevre dokuları istila etmesi için immünolojik olarak duyarlı bir mikro ortam sağlar. Özellikle indoleamin 2,3-dioksijenaz 1 aşırı aktivasyonunun gastrointestinal kanserler, jinekolojik kanserler, hematolojik maligniteler, meme kanseri, akciğer kanseri, glioma, melanom, prostat ve pankreas kanseri gibi çeşitli kanserlerde hastalığın patogenezinin ve kötü prognozunun bir belirleyicisi olarak rol oynadığı düşünülmektedir. Ek olarak, kinürenik asitin, beyin omurilik sıvısındaki kinolinik asit konsantrasyonlarını artırarak inflamasyona yol açtığı ve depresif semptomlara yol açtığı gösterilmiştir. Bu bağlamda tümör oluşumu, prognozu, kanserin kendisine veya tedavilerine bağlı oluşan yan etkilerin açıklanmasında kinürenin yolağı metabolitleri ile ilgili araştırmalar hız kazanmıştır. Önceki çalışmalarda hem akut hem de kronik egzersizin, çeşitli hastalıklarda (diyabet, depresyon, multiple skleroz gibi) kinürenin yolağı enzimleri ve metabolitleri üzerine up/down regülasyona neden olabileceği gösterilmiştir. Kinürenin yolağının mediatörü olarak egzersizin etkinliğini kanser alanında araştıran çalışma sayısı oldukça kısıtlıdır. Bu geleneksel derlemede, kinürenin yolağının egzersize bağlı modülasyonları ile ilgili mevcut bilgiler, altta yatan mekanizmalar ayrıca egzersizle indüklenen kinürenin yolağı ve egzersiz/kanser ilişkisi incelenecektir.

Keywords

• Kinürenin triptofan
• kanser
• egzersiz

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