One-Carbon and Polyamine Metabolism as Cancer Therapy Targets

Islam, Anowarul; Shaukat, Zeeshan; Hussain, Rashid; Gregory, Stephen L.

doi:10.3390/biom12121902

Cited by 10 publications

(3 citation statements)

References 269 publications

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“…The present study showed that the expression level of CF was downregulated in the CTX group and normalized after treatment by GLPP and LMS. In the methionine cycle, the one-carbon unit can be used for homocysteine remethylation to regenerate methionine ( 42 , 43 ). In the present study, L-cysteine, which is involved in the methionine cycle, was significantly upregulated in the CTX group, and L-cysteine and 5-deoxy-5-methylthioadenosine were normalized after the treatment of GLPP.…”

Section: Discussionmentioning

confidence: 99%

Effects of Ganoderma lucidum polysaccharide peptide ameliorating cyclophosphamide-induced immune dysfunctions based on metabolomics analysis

Xie

Lin

et al. 2023

Front. Nutr.

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Ganoderma lucidum polysaccharide peptide (GLPP) is one of the most abundant constituents of Ganoderma lucidum (G. lucidum), with a wide range of functional activities. The present study investigated the immunomodulatory effects of GLPP in cyclophosphamide (CTX)-induced immunosuppressive mice. The results showed that 100 mg/kg/day of GLPP administration significantly alleviated CTX-induced immune damage by improving immune organ indexes, earlap swelling rate, the index of carbon phagocytosis and clearance value, secretion of cytokines (TNF-α, IFN-γ, and IL-2), and immunoglobulin A(IgA) in the mice. Furthermore, ultra-performance liquid chromatography with mass/mass spectrometry (UPLC-MS/MS) was conducted to identify the metabolites, followed by biomarker and pathway analysis. The results showed that GLPP treatment alleviated CTX-induced alterations in the fecal metabolome profile, including arachidonic acid (AA), leukotriene D4 (LTD4), indole-3-ethanol, and formyltetrahydrofolate (CF), by reversing citric acid, malic acid, cortisol, and oleic acid. These results support the concept that GLPP exhibits immunomodulatory activity via the folate cycle, methionine cycle, TCA cycle, fatty acid biosynthesis and metabolism, glycerophospholipid metabolism, AA metabolism, and cAMP pathways. In conclusion, the results could be helpful to understand the use of GLPP to clarify the immunomodulatory mechanism and be used as immunostimulants to prevent CTX-induced side effects in the immune system.

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Section: Discussionmentioning

confidence: 99%

Effects of Ganoderma lucidum polysaccharide peptide ameliorating cyclophosphamide-induced immune dysfunctions based on metabolomics analysis

Xie

Lin

et al. 2023

Front. Nutr.

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“…1C metabolism provides the precursors for nucleotide, protein, sphingolipid and phospholipid synthesis. 198 The proliferation and growth of cancer cells rely, to some extent, on the availability of 1C units, suggesting that restricting the supplementation of 1C can yield more clinical benefits. Based on this theory, several 1C metabolismtargeting drugs have been developed, including pemetrexed, methotrexate and 5-FU.…”

Section: Prospective and Challenges Of Targeting 1c Metabolismmentioning

confidence: 99%

Targeting one‐carbon metabolism for cancer immunotherapy

Ren,

Wang,

Zheng

et al. 2024

Clinical & Translational Med

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BackgroundOne‐carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic pathways, including nucleotide metabolism, amino acid metabolism, cellular redox defence and epigenetic maintenance. At present, 1C metabolism is considered the hallmark of cancer. The 1C units obtained from the metabolic pathways increase the proliferation rate of cancer cells. In addition, anticancer drugs, such as methotrexate, which target 1C metabolism, have long been used in the clinic. In terms of immunotherapy, 1C metabolism has been used to explore biomarkers connected with immunotherapy response and immune‐related adverse events in patients.MethodsWe collected numerous literatures to explain the roles of one‐carbon metabolism in cancer immunotherapy.ResultsIn this review, we focus on the important pathways in 1C metabolism and the function of 1C metabolism enzymes in cancer immunotherapy. Then, we summarise the inhibitors acting on 1C metabolism and their potential application on cancer immunotherapy. Finally, we provide a viewpoint and conclusion regarding the opportunities and challenges of targeting 1C metabolism for cancer immunotherapy in clinical practicability in the future.ConclusionTargeting one‐carbon metabolism is useful for cancer immunotherapy.

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“…The B vitamins (including vitamin B 1 , B 2 , B 6 , B 9 , and B 12 ) play important roles as cofactors in various biological processes, such as tissue metabolism, cellular stress responses, signal transduction pathways, and gene expression regulation [ 12 , 13 , 14 ]. The relationship between B vitamin levels and the development and progression of lung cancer has been a popular topic, but the results remain inconclusive [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Positive Association of Serum Vitamin B6 Levels with Intrapulmonary Lymph Node and/or Localized Pleural Metastases in Non-Small Cell Lung Cancer: A Retrospective Study

Liu

Bai

et al. 2023

Nutrients

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The relationship between vitamin B levels and the development and progression of lung cancer remains inconclusive. We aimed to investigate the relationship between B vitamins and intrapulmonary lymph nodes as well as localized pleural metastases in patients with non-small cell lung cancer (NSCLC). This was a retrospective study including patients who underwent lung surgery for suspected NSCLC at our institution from January 2016 to December 2018. Logistic regression models were used to evaluate the associations between serum B vitamin levels and intrapulmonary lymph node and/or localized pleural metastases. Stratified analysis was performed according to different clinical characteristics and tumor types. A total of 1498 patients were included in the analyses. Serum vitamin B6 levels showed a positive association with intrapulmonary metastasis in a multivariate logistic regression (odds ratio (OR) of 1.016, 95% confidence interval (CI) of 1.002–1.031, p = 0.021). After multivariable adjustment, we found a high risk of intrapulmonary metastasis in patients with high serum vitamin B6 levels (fourth quartile (Q4) vs. Q1, OR of 1.676, 95%CI of 1.092 to 2.574, p = 0.018, p for trend of 0.030). Stratified analyses showed that the positive association between serum vitamin B6 and lymph node metastasis appeared to be stronger in females, current smokers, current drinkers, and those with a family history of cancer, squamous cell carcinoma, a tumor of 1–3 cm in diameter, or a solitary tumor. Even though serum vitamin B6 levels were associated with preoperative NSCLC upstaging, B6 did not qualify as a useful biomarker due to weak association and wide confidence intervals. Thus, it would be appropriate to prospectively investigate the relationship between serum vitamin B6 levels and lung cancer further.

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One-Carbon and Polyamine Metabolism as Cancer Therapy Targets

Cited by 10 publications

References 269 publications

Effects of Ganoderma lucidum polysaccharide peptide ameliorating cyclophosphamide-induced immune dysfunctions based on metabolomics analysis

Effects of Ganoderma lucidum polysaccharide peptide ameliorating cyclophosphamide-induced immune dysfunctions based on metabolomics analysis

Targeting one‐carbon metabolism for cancer immunotherapy

Positive Association of Serum Vitamin B6 Levels with Intrapulmonary Lymph Node and/or Localized Pleural Metastases in Non-Small Cell Lung Cancer: A Retrospective Study

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