Amino Acid Metabolism in Cancer Drug Resistance

“…It has been reported that amino acid metabolism is related to drug resistance in cancer cells, as it regulates the TCA cycle and oxidative phosphorylation [ 45 ]. Additionally, several reports have indicated that inhibiting mTOR signaling can increase the sensitivity to paclitaxel [ 46 , 47 , 48 ].…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Glutamine Uptake Resensitizes Paclitaxel Resistance in SKOV3-TR Ovarian Cancer Cell via mTORC1/S6K Signaling Pathway

Kim

Jang²,

Kim³

et al. 2022

IJMS

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Ovarian cancer is a carcinoma that affects women and that has a high mortality rate. Overcoming paclitaxel resistance is important for clinical application. However, the effect of amino acid metabolism regulation on paclitaxel-resistant ovarian cancer is still unknown. In this study, the effect of an amino acid-deprived condition on paclitaxel resistance in paclitaxel-resistant SKOV3-TR cells was analyzed. We analyzed the cell viability of SKOV3-TR in culture conditions in which each of the 20 amino acids were deprived. As a result, the cell viability of the SKOV3-TR was significantly reduced in cultures deprived of arginine, glutamine, and lysine. Furthermore, we showed that the glutamine-deprived condition inhibited mTORC1/S6K signaling. The decreased cell viability and mTORC1/S6K signaling under glutamine-deprived conditions could be restored by glutamine and α-KG supplementation. Treatment with PF-4708671, a selective S6K inhibitor, and the selective glutamine transporter ASCT2 inhibitor V-9302 downregulated mTOR/S6K signaling and resensitized SKOV3-TR to paclitaxel. Immunoblotting showed the upregulation of Bcl-2 phosphorylation and a decrease in Mcl-1 expression in SKOV3-TR via the cotreatment of paclitaxel with PF-4708671 and V-9302. Collectively, this study demonstrates that the inhibition of glutamine uptake can resensitize SKOV3-TR to paclitaxel and represents a promising therapeutic target for overcoming paclitaxel resistance in ovarian cancer.

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“…Glutamin hücre biyolojisinde pleiotropik bir role sahiptir ve çeşitli kanser türlerinde bağımlılığı iyi bilinmektedir. Ayrıca, farmakolo jik müdahale veya glutamin metabolizmasının diyet modülasyonu umut verici bir terapötik yaklaşım olarak kabul edilir (23,24). Arjinin; yarı esansiyel bir amino asit olup, kanser hücresi büyümesi ve hayatta kalma ve bağışıklık hücresi işlevi gibi çeşitli biyolojik işlevlerde yer alır.…”

Section: Discussionunclassified

“…Arjinin; yarı esansiyel bir amino asit olup, kanser hücresi büyümesi ve hayatta kalma ve bağışıklık hücresi işlevi gibi çeşitli biyolojik işlevlerde yer alır. Bu nedenle, arginin mevcudiyetinin modülasyonu, metabolizmaya dayalı kanser tedavileri için umut verici bir terapötik strateji olarak vurgulanmaktadır (24).Yaptığımız çalışma sonucunda; sisplatin kanser hücrelerinde argininve glutamin aminoasitlerinde artışa yol açarken, normal hücrelerde bu aminoasitlerin azalmasına neden olmuştur.Sonuç olarak, kanserlerde ilaç direncini artırmada amino asit metabolizmasının temel rollerine ilişkin bilgiler, ilaç direncinin üstesinden gelmek için potansiyel terapötik yaklaşımları ortaya çıkarmıştır. Konvansiyonel kemoterapi ve ilgili toksisitenin gerekliliğini azaltmaya yardımcı olmak için amino asit metabolizmasının modülasyonu hakkında daha fazla araştırma yapılacağını umuyoruz.…”

Section: Discussionunclassified

Cisplatin’in Normal ve Prostat Kanseri Hücrelerinin Aminoasit Metabolizması Üzerine Etkileri

Arslan

Temiz

Akmeşe

et al. 2022

Harran Üniversitesi Tıp Fakültesi Dergisi

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Background: Prostate cancer, which is a type of cancer affecting the male reproductive system, is the second most common type of cancer worldwide and constitutes 10% of all cancers in men. One of the primary treatment methods used in prostate cancer patients is chemotherapy. Cisplatin is a chemotherapy drug widely used in the treatment of many types of cancer, especially prostate cancer, and it acts by interfering with DNA replication and transcription processes. However, drug resistance against cisplatin in cancer cells and side effects on normal cells limit its use and reduce the treatment efficiency. Recently, resistance to cisplatin in cancer cells has been reported to be due to "metabolic reprogramming". Targeting metabolic processes therefore represents a potential new strategy to reverse cisplatin resistance. Materials and Methods: This study investigates the effects of cisplatin on amino acid metabolism of cancerous and normal prostate cells. In the study, 10 µM cisplatin was applied to prostate cancer cells (DU-145) and normal prostate cells (PNT-1A) in the medium and incubated for 24 hours. The free amino acid profile in the obtained cell lysate was analyzed by LC-MS/MS method. Data analysis was done with SPSS and metaboanalyst 5.0 program. Results: While the amount of arginine decreased in the PNT1A cells treated with cisplatin, the levels of taurine, phosphoethonalamine, ornithine and tryptophan were increased. It was determined that the amount of arginine, glycine and 2-Aminoheptandioic Acid increased, while sarcosine and beta alanine decreased in DU-145 cells when treated with cisplatin. Conclusions: As a result of the study, cisplatin has different effects on amino acid metabolism of normal and cancer cells, therefore, new studies by applying different amino acids in vitro may have positive effects in cancer treatment.

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Amino Acid Metabolism in Cancer Drug Resistance

Cited by 64 publications

References 149 publications

Metabolomics studies of cell–cell interactions using single cell mass spectrometry combined with fluorescence microscopy

Metabolomics studies of cell–cell interactions using single cell mass spectrometry combined with fluorescence microscopy

Inhibition of Glutamine Uptake Resensitizes Paclitaxel Resistance in SKOV3-TR Ovarian Cancer Cell via mTORC1/S6K Signaling Pathway

Cisplatin’in Normal ve Prostat Kanseri Hücrelerinin Aminoasit Metabolizması Üzerine Etkileri

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