scholarly journals NDRG2 Inhibits Pyruvate Carboxylase-Mediated Anaplerosis and Combines with Glutamine Blockade To Inhibit The Growth of Glioma

2021 ◽  
Author(s):  
Jiancai Wang ◽  
Xiang Sun ◽  
Jiayuan Wang ◽  
Kun Zhang ◽  
Yiyi Yuan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Pyruvate Carboxylase ◽  
Affinity Purification ◽  
Glioma Cells ◽  
Tissue Microarrays ◽  
Gas Chromatography Mass Spectrometry ◽  
Mouse Tumors ◽  
Idh1 R132h

Abstract Background Due to the rapid proliferation, cancer cells have increased anabolic biosynthesis, which requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the catalysis of pyruvate carboxylase (PC) and glutaminase (GLS) respectively. In GLS-suppressed cancer cells, the PC-mediated pathway for anaplerosis is crucial to maintain cell growth and proliferation. Here, we investigated the regulatory role and molecular mechanism of the tumor suppressor NDRG2 in PC and PC-mediated anaplerosis. Methods We first evaluated the correlation between PC and NDRG2 in glioma cell lines and human glioma tissue microarrays. The interaction between PC and NDRG2 was tested by tandem affinity purification-mass spectrometry (TAP-MS) and coimmunoprecipitation (Co-IP). We then detected the effect of NDRG2 on PC-mediated anaplerosis by gas chromatography-mass spectrometry (GC-MS). Preclinical evaluation of NDRG2 alone or combined with a glutaminase inhibitor was conducted in glioma cells and xenograft mouse tumors. Results NDRG2 interacted with PC and induced the degradation of PC in glutamine-deficient glioma cells. NDRG2 also inhibited the activity of PC and PC-mediated anaplerosis. As a result, NDRG2 significantly inhibited the malignant growth and proliferation of glioma cells in combination with a glutamine antagonist. In addition, NDRG2 more significantly inhibited the protein level of PC in IDH1(R132H)-mutant glioma cells than in wild-type glioma cells. Conclusions These findings indicate that the molecular mechanism of NDRG2 inhibits PC-mediated anaplerosis and collaborates with glutamine antagonist to inhibit the malignant proliferation of glioma cells, thus providing a theoretical and experimental basis for targeting anaplerosis in glioma therapy.

scholarly journals Analysis of the essential oil from Lantana camara leaves and its cytotoxic potential against T-47D breast cancer cells

2021 ◽  
Vol 12 (1) ◽  
pp. 1-9
Author(s):  
Suryati Suryati ◽  
Enda Desriansyah Aziz ◽  
Mai Efdi ◽  
Fatma Sri Wahyuni ◽  
Dira Hefni
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Essential Oil ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Artemia Salina ◽  
Lantana Camara ◽  
Gas Chromatography Mass Spectrometry ◽  
Cytotoxic Potential ◽  
Main Compound

Lantana camara Linn is a family of Verbenaceae which grows wild and is widespread in various both tropical and sub-tropical countries. Isolation essential oil of the L. camara leaves extracted by hydrodistillation and were analyzed by Gas Chromatography-Mass Spectrometry (GC-MS). The results of GC-MS analysis show isocaryophyllene (14.39%), ρ-cymene (8.17 %), β-cubebene (7.8 %), α-pinene (7.64 %), and β-elemene (5.51 %) as the main compound. The cytotoxic activity of the isolated essential oil was highly toxic both to Artemia salina shrimp larvae (LC50 15.92 µg/mL) and to breast cancer cells T-47D (IC50 10.67 µM).

Substrate cycling between pyruvate and oxaloacetate in awake normal and 3,3'-5-triiodo-L-thyronine-treated rats

1994 ◽  
Vol 267 (2) ◽  
pp. E273-E277 ◽  
Author(s):  
K. F. Petersen ◽  
G. W. Cline ◽  
J. B. Blair ◽  
G. I. Shulman
Keyword(s):  
Mass Spectrometry ◽  
Nuclear Magnetic Resonance ◽  
Enzyme Activity ◽  
Malic Enzyme ◽  
Pyruvate Carboxylase ◽  
Activity Ratio ◽  
Gas Chromatography Mass Spectrometry ◽  
Resonance Spectroscopy ◽  
Liver Enzyme Activity ◽  
1H Nuclear Magnetic Resonance

Substrate cycling between pyruvate and oxaloacetate was assessed in awake 24-h fasted normal and triiodothyronine (T3)-treated rats. After a 20- or 60-min infusion of [3-13C]alanine (99% enriched, 12 mg/min) the 13C enrichments of liver glucose and alanine carbons were analyzed by 13C and 1H nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry. Substrate cycling from phosphoenolpyruvate to pyruvate [via pyruvate kinase (PK)] and from oxaloacetate to pyruvate [via malic enzyme (ME)] relative to the pyruvate carboxylase (PC) flux [i.e., (PK+ME)/PC] was assessed by the ratio of the 13C enrichment of C-2 alanine relative to that in C-5 glucose. In the normal rats (PK+ME)/PC was 0.26 +/- 0.07 (n = 7, t = 20 min) and 0.37 +/- 0.08 (n = 4, t = 60 min). In the T3-treated rats the (PK+ME)/PC increased four- to fivefold to 1.03 +/- 0.19 (n = 8, t = 20 min) and to 1.83 +/- 0.19 (n = 3, t = 60 min) (P < 0.05 vs. normal rats). The liver enzyme activity of PK did not change with T3 treatment (normal 14.22 +/- 5.25 U/g liver vs. T3 treated 13.40 +/- 1.10 U/g liver), whereas both the enzyme activity ratio of PK (normal 0.47 +/- 0.15 vs. T3 treated 0.77 +/- 0.03, P < 0.05) and the activity of ME (normal 0.89 +/- 0.30 U/g liver vs. T3 treated 4.25 +/- 0.60 U/g liver, P < 0.05) increased with T3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

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