Emerging role of inositol monophosphatase in cancer

Chen, Qian; Shen, Liangfang; Li, Shan

doi:10.1016/j.biopha.2023.114442

Cited by 3 publications

(2 citation statements)

References 82 publications

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“…Besides the entry of amino acids into the TCA cycle, we suggest that the biosynthesis of protective proteins against enhanced oxidative stress may also occur in Pd 2 Spm/R cells. This is supported by increased GSH and taurine (perhaps related to increased m -inositol, also reported to have antioxidant activity), , which may work to significantly reduce the NAD + /NADH ratio, in contrast with Pd 2 Spm/S cells (where such mechanism did not seem as efficient). Similarly to cDDP/R cells, increased levels of choline compounds are observed in Pd 2 Spm/R cells; such a signature seems to be a general characteristic of R cells, irrespective of the treatment.…”

Section: Discussionmentioning

confidence: 99%

Pd₂Spermine as an Alternative Therapeutics for Cisplatin-Resistant Triple-Negative Breast Cancer

Carneiro,

Batista de Carvalho,

Vojtek

et al. 2024

J. Med. Chem.

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Cisplatin (cDDP) resistance is a matter of concern in triple-negative breast cancer therapeutics. We measured the metabolic response of cDDP-sensitive (S) and -resistant (R) MDA-MB-231 cells to Pd 2 Spermine(Spm) (a possible alternative to cDDP) compared to cDDP to investigate (i) intrinsic response/ resistance mechanisms and (ii) the potential cytotoxic role of Pd 2 Spm. Cell extracts were analyzed by untargeted nuclear magnetic resonance metabolomics, and cell media were analyzed for particular metabolites. CDDP-exposed S cells experienced enhanced antioxidant protection and small deviations in the tricarboxylic acid cycle (TCA), pyrimidine metabolism, and lipid oxidation (proposed cytotoxicity signature). R cells responded more strongly to cDDP, suggesting a resistance signature of activated TCA cycle, altered AMP/ADP/ATP and adenine/uracil fingerprints, and phospholipid biosynthesis (without significant antioxidant protection). Pd 2 Spm impacted more markedly on R/S cell metabolisms, inducing similarities to cDDP/S cells (probably reflecting high cytotoxicity) and strong additional effects indicative of amino acid depletion, membrane degradation, energy/ nucleotide adaptations, and a possible beneficial intracellular γ-aminobutyrate/glutathione-mediated antioxidant mechanism.

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Section: Discussionmentioning

confidence: 99%

Pd₂Spermine as an Alternative Therapeutics for Cisplatin-Resistant Triple-Negative Breast Cancer

Carneiro,

Batista de Carvalho,

Vojtek

et al. 2024

J. Med. Chem.

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“…In benign tissues close to aggressive tumors, the levels of myo-inositol were also elevated. This metabolite is involved in many biological processes ranging from intracellular signal transduction, calcium homeostasis regulation to energy metabolism, and it is essential for cancer formation and metastasis (35, 36). Using prostate tissue extracts, inositol hexaphosphate (IP6) was shown to significantly decrease glucose metabolism and membrane phospholipid synthesis, in addition to causing an increase in myo-inositol levels in the prostate (37).…”

Section: Discussionmentioning

confidence: 99%

Metabolic readouts of tumor instructed normal tissues (TINT) identify aggressive prostate cancer subgroups for tailored therapy

Dudka,

Wikström,

Bergh

et al. 2024

Preprint

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Background: Prostate cancer (PC) diagnosis relies on histopathological examination of prostate biopsies, which is restricted by insufficient sampling of all tumors present. Including samples from non-PC but tumor instructed normal tissues (TINT) may increase the diagnostic power by exploring the adaptive responses in benign tissues near tumors. Methods: Here, we applied high-resolution magic angle spinning nuclear magnetic resonance (HR MAS NMR) to identify metabolomic biomarkers with high diagnostic value in benign prostate tissues near low/high-grade tumors. Results: Benign samples near high-grade tumors (B ISUP 3+4) exhibit altered metabolic profiles compared to those close to low-grade tumors (B ISUP 1+2). The levels of six metabolites were significantly different between the two groups; myo-inositol, lysine, serine and combined signal of lysine/leucine/arginine were increased in benign samples near high-grade tumors (B ISUP 3+4) compared to near low-grade tumors (B ISUP 1+2), while levels of ethanolamine and lactate decreased. Additionally, we revealed metabolic differences in non-cancer tissues as a function of their distance to the nearest tumor. Eight metabolites (glutathione, glutamate, combined signal of glutamate/glutamine - glx, glycerol, inosine, ethanolamine, serine and arginine) significantly differentiated between benign tissue located close to the tumor (d ≤ 5 mm) compared to those far away (d ≥ 1 cm). Conclusions: Our HR MAS NMR-based approach identified metabolic signatures in prostate biopsies that reflect the response of benign tissues to the presence of nearby located tumors in the same prostate and confirmed the power of the TINT concept for improved PC diagnostics and understanding of tumor-tissue interactions.

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Pathogenesis or a response to lithium? A novel perspective for mitochondrial mass fluctuation of naïve T cells in patients with bipolar disorder

Chen,

Wang,

Huang

et al. 2024

Journal of Affective Disorders

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Emerging role of inositol monophosphatase in cancer

Cited by 3 publications

References 82 publications

Pd₂Spermine as an Alternative Therapeutics for Cisplatin-Resistant Triple-Negative Breast Cancer

Pd₂Spermine as an Alternative Therapeutics for Cisplatin-Resistant Triple-Negative Breast Cancer

Metabolic readouts of tumor instructed normal tissues (TINT) identify aggressive prostate cancer subgroups for tailored therapy

Pathogenesis or a response to lithium? A novel perspective for mitochondrial mass fluctuation of naïve T cells in patients with bipolar disorder

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Emerging role of inositol monophosphatase in cancer

Cited by 3 publications

References 82 publications

Pd2Spermine as an Alternative Therapeutics for Cisplatin-Resistant Triple-Negative Breast Cancer

Pd2Spermine as an Alternative Therapeutics for Cisplatin-Resistant Triple-Negative Breast Cancer

Metabolic readouts of tumor instructed normal tissues (TINT) identify aggressive prostate cancer subgroups for tailored therapy

Pathogenesis or a response to lithium? A novel perspective for mitochondrial mass fluctuation of naïve T cells in patients with bipolar disorder

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Pd₂Spermine as an Alternative Therapeutics for Cisplatin-Resistant Triple-Negative Breast Cancer

Pd₂Spermine as an Alternative Therapeutics for Cisplatin-Resistant Triple-Negative Breast Cancer