Serdemetan Antagonizes the Mdm2-HIF1α Axis Leading to Decreased Levels of Glycolytic Enzymes

Lehman, Jason A.; Hauck, Paula M.; Gendron, Jaimie M.; Batuello, Christopher N.; Eitel, Jacob; Albig, Allan R.; Kadakia, Madhavi; Mayo, Lindsey D.

doi:10.1371/journal.pone.0074741

Cited by 9 publications

(6 citation statements)

References 15 publications

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“…A previous study revealed that M-CSF-induced 5-FU resistance was mediated by decreasing the expression of MDM2 and ABCB1. In addition, MDM2 induced upregulation of HIF-1α protein in a p53-independent manner (13). Therefore, M-CSF suppressed the expression of HIF-1α through a p53-independent pathway.…”

Section: Discussionmentioning

confidence: 91%

“…A recent study revealed that HIF-1α regulated anti-apoptotic genes, which ultimately led to increased tumour growth and drug resistance (11). Murine double minute 2 (MDM2), is an oncogene that is upstream of HIF-1α and regulates the expression of HIF-1α (12,13). M-CSF was revealed to directly decrease the expression of MDM2, further contributing to drug resistance in tumour treatments (5).…”

Section: Introductionmentioning

confidence: 99%

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Cytoplasmic M‑CSF facilitates apoptosis resistance by inhibiting the HIF‑1α/BNIP3/Bax signalling pathway in MCF‑7 cells

Zhang

Liu

et al. 2018

Oncol Rep

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Macrophage colony-stimulating factor (M-CSF), a tumour marker, is related to tumour cell anti-apoptosis and drug resistance. However, the role of M-CSF in MCF-7 cells is unknown. In the present study, the effect and mechanism of M-CSF on hypoxia-inducible factor-1α (HIF-1α)/BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/Apoptosis Regulator BAX signalling in human breast cancer MCF-7 cells were investigated. Western blotting revealed that the expression of HIF-1α, BNIP3, Bax, caspase-3 and caspase-9 was lower in MCF-7-M cells compared to MCF-7 and MCF-7-C cells treated with adriamycin (ADM). Immunoprecipitation combined with western blotting was used to detect the interaction between Bcl-2 and BNIP3 or Bax protein. MCF-7-M cells had a higher amount of Bax binding to Bcl-2 compared to MCF-7 cells or MCF-7-C cells, while the amount of BNIP3 binding to Bcl-2 was decreased in MCF-7-M cells. Hoechst 33342 staining and flow cytometry were utilized to evaluate the effect of M-CSF on apoptosis in MCF-7 cells treated with ADM. Compared to ADM-treated MCF-7 cells, the apoptotic rate of MCF-7-M cells was significantly decreased. These effects were dependent on the concentration of ADM. In conclusion, cytoplasmic M-CSF suppressed apoptosis by inhibiting the HIF-1α/BNIP3/Bax signalling pathway, which potentiated the dissociation of Bcl-2 from Bcl-2-BNIP3 compounds and the formation of Bcl-2-Bax compounds.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Cytoplasmic M‑CSF facilitates apoptosis resistance by inhibiting the HIF‑1α/BNIP3/Bax signalling pathway in MCF‑7 cells

Zhang

Liu

et al. 2018

Oncol Rep

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“…Next to this most notable finding we also observed a less strong correlation of Decitabine sensitivity with sensitivity to various unrelated drugs, i.e. the thymidylate synthetase inhibitor 5-Fluorouracil (Longley et al 2003 ), the cholesterol transport inhibitor and MDM2-antagonist Serdemetan (Lehman et al 2013 ; Jones et al 2013 ), the EGF-receptor- and HER2-inhibitor Lapatinib (Huang and Rizzo 2012 ) and the PARP-inhibitor Veliparib (Glendenning and Tutt 2011 ). Some of these drugs additionally correlated with each other.…”

Section: Discussionmentioning

confidence: 76%

Understanding drugs in breast cancer through drug sensitivity screening

et al. 2015

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With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-015-1406-8) contains supplementary material, which is available to authorized users.

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“… 34 Similar biological effects were also observed in IDH1R 132 H mutant or Ras knockdown glioma cells via the HIF-1α/GLUT1 axis. 28 , 90 , 91 Besides, miRNA-451, targeting recombinant human calcium binding protein 39 (CAB39) to regulate GLUT1 inhibited the glucose metabolism, the proliferation, and invasion of glioma cells. 84 Similarly, miR-495 increased GLUT1 to promote glucose uptake and lactate production in glioma.…”

Section: Implication Of Key Enzymes and Gluts In Aerobic Glycolysismentioning

confidence: 99%

<p>Emerging Roles and Therapeutic Interventions of Aerobic Glycolysis in Glioma</p>

Han¹,

Shi²,

Cao³

et al. 2020

OTT

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Glioma is the most common type of intracranial malignant tumor, with a great recurrence rate due to its infiltrative growth, treatment resistance, intra-and intertumoral genetic heterogeneity. Recently, accumulating studies have illustrated that activated aerobic glycolysis participated in various cellular and clinical activities of glioma, thus influencing the efficacy of radiotherapy and chemotherapy. However, the glycolytic process is too complicated and ambiguous to serve as a novel therapy for glioma. In this review, we generalized the implication of key enzymes, glucose transporters (GLUTs), signalings and transcription factors in the glycolytic process of glioma. In addition, we summarized therapeutic interventions via the above aspects and discussed promising clinical applications for glioma.

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Serdemetan Antagonizes the Mdm2-HIF1α Axis Leading to Decreased Levels of Glycolytic Enzymes

Cited by 9 publications

References 15 publications

Cytoplasmic M‑CSF facilitates apoptosis resistance by inhibiting the HIF‑1α/BNIP3/Bax signalling pathway in MCF‑7 cells

Cytoplasmic M‑CSF facilitates apoptosis resistance by inhibiting the HIF‑1α/BNIP3/Bax signalling pathway in MCF‑7 cells

Understanding drugs in breast cancer through drug sensitivity screening

<p>Emerging Roles and Therapeutic Interventions of Aerobic Glycolysis in Glioma</p>

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