Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

Shen, Yonghua; Chen, Min; Huang, Shenglan; Zou, Xiaoping

doi:10.3892/ol.2015.3912

Cited by 23 publications

(12 citation statements)

References 32 publications

(36 reference statements)

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“…In accordance with our metabolic data, the decrease in phenylalanine or increase in alanine also contributes to enhanced aerobic glycolysis in tumor cells because these amino acids might act as allosteric inhibitors to the tetramer conformations of PKM1 or PKM2 [50]. PKM2 elevation might contribute to radiation resistance or poor prognosis in patients with cervical carcinoma and oral SCC, whereas reduced PKM2 expression is associated with the inhibition of cell proliferation and EMT progression or enhanced radiation sensitivity in cancer cells [51][52][53]. These findings indicate that the detected increase in PKM2 in cervical cancer and precancerous lesions is likely associated with enhanced aerobic glycolysis and tumor growth.…”

Section: Discussionsupporting

confidence: 76%

Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection

Abudula¹,

Rouzi²,

Xu³

et al. 2019

Bosn J of Basic Med Sci

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Aberrant metabolic regulation has been observed in human cancers, but the corresponding regulation in human papillomavirus (HPV) infection-associated cervical cancer is not well understood. Here, we explored potential biomarkers for the early prediction of cervical carcinoma based on the metabolic profile of uterine cervical tissue specimens that were positive for HPV16 infection. Fifty-two fresh cervical tissues were collected from women confirmed to have cervical squamous cell carcinoma (SCC; n = 21) or cervical intraepithelial neoplasia (CIN) stages II-III (n = 20). Eleven healthy women constituted the controls (negative controls [NCs]). Real-time polymerase chain reaction (PCR) was performed to detect HPV infection in the tissues. High-resolution magic angle spinning nuclear magnetic resonance was utilized for the analysis of the metabolic profile in the tissues. The expression of rate-limiting enzymes involved in key metabolic pathways was detected by reverse-transcription quantitative PCR. An independent immunohistochemical analysis was performed using 123 cases of paraffin-embedded cervical specimens. A profile of 17 small molecular metabolites that showed differential expression in HPV16-positive cervical SCC or CIN II-III compared with HPV-negative NC group was identified. According to the profile, the levels of α-and β-glucose decreased, those of lactate and low-density lipoproteins increased, and the expression of multiple amino acids was altered. Significantly increased transcript and protein levels of glycogen synthase kinase 3 beta (GSK3β) and glutamate decarboxylase 1 (GAD1) and decreased transcript and protein levels of pyruvate kinase muscle isozyme 2 (PKM2) and carnitine palmitoyltransferase 1A (CPT1A) were observed in the patient group (p < 0.05). HPV infection and cervical carcinogenesis drive metabolic modifications that might be associated with the aberrant regulation of enzymes related to metabolic pathways.

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Section: Discussionsupporting

confidence: 76%

Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection

Abudula¹,

Rouzi²,

Xu³

et al. 2019

Bosn J of Basic Med Sci

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“…PPIs substantially disrupt the acidic microenvironment and suppress phosphorylation of the extracellular signal that regulates kinase 1/2, Akt/Src kinases, and pyruvate kinase M2. Consequently, apoptosis or inhibition in cancer cell development may be induced …”

Section: Discussionmentioning

confidence: 99%

Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population‐Based Study

Chen

Lee

Lin

et al. 2018

The Journal of Clinical Pharma

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Although current evidence suggests potential antitumor activity of proton pump inhibitors (PPIs), there is no population-based evidence of an association between PPI use and subsequent breast cancer risks. We used an observational case-control study to examine the association between prior PPI use and breast cancer occurrence. Additional analysis examined dose-response and age-stratified associations of PPIs with breast cancer. This study used data from the Taiwan National Health Insurance Research Dataset. A total of 64,234 women diagnosed with breast cancer between 2004 and in 2013 were selected as cases. Controls were 64,234 women without cancer who were selected by matching them with cases on the basis of sociodemographic characteristics and widely prevalent comorbidities. Each study subject's claims data were tracked back for 5 years to determine precancer prescriptions of PPIs. Logistic regression modeling was used for the analysis. A total of 11,871 (9.24%) women had used PPIs within the prior 5 years, 8.06% and 10.42% among cases and controls, respectively. Breast cancer patients were 25% less likely to have had prior PPI exposure after adjustment for comorbidities that predispose to PPI exposure (95%CI 0.72-0.78) in the risk of breast cancer occurrence. A dose-response effect was also detected, with the highest effect, 35% lower PPI odds (95%CI 0.61-0.70) among patients in the highest exposure category. Our findings may suggest that women at a higher-than-average risk of breast cancer may benefit from PPI prescriptions if they have medical conditions that could benefit from PPIs.

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“…Lastly, we showed that acidity represents a potent mechanism of tumor immune escape, and that PPIs increase the immune reaction against tumors [ 25 , 44 , 100 ]. Beside the direct toxic effects, PPIs were also able to inhibit mTOR signaling and other metabolic pathways in gastric carcinoma cell line, and to potentiate the antitumor effectiveness of Adriamycin in mice harboring gastric carcinoma xenografts [ 101 , 102 , 103 , 104 , 105 , 106 ]. In gastric cancer models, PPIs induced cancer stem cell depletion which passed through inhibition of proliferation, sphere formation, and 5-fluorouracil chemoresistance [ 107 ].…”

Section: V-atpase Inhibitorsmentioning

confidence: 99%

Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy

et al. 2017

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Microenvironmental acidity is becoming a key target for the new age of cancer treatment. In fact, while cancer is characterized by genetic heterogeneity, extracellular acidity is a common phenotype of almost all cancers. To survive and proliferate under acidic conditions, tumor cells up-regulate proton exchangers and transporters (mainly V-ATPase, Na+/H+ exchanger (NHE), monocarboxylate transporters (MCTs), and carbonic anhydrases (CAs)), that actively extrude excess protons, avoiding intracellular accumulation of toxic molecules, thus becoming a sort of survival option with many similarities compared with unicellular microorganisms. These systems are also involved in the unresponsiveness or resistance to chemotherapy, leading to the protection of cancer cells from the vast majority of drugs, that when protonated in the acidic tumor microenvironment, do not enter into cancer cells. Indeed, as usually occurs in the progression versus malignancy, resistant tumor clones emerge and proliferate, following a transient initial response to a therapy, thus giving rise to more malignant behavior and rapid tumor progression. Recent studies are supporting the use of a cocktail of proton exchanger inhibitors as a new strategy against cancer.

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Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

Cited by 23 publications

References 32 publications

Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection

Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection

Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population‐Based Study

Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy

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