Targeting glycometabolic reprogramming to restore the sensitivity of leukemia drug-resistant K562/ADM cells to adriamycin

Zhang, Xueyan; Chen, Jing; Ai, Ziying; Zhang, Zhewen; Lin, Li; Wei, Hulai

doi:10.1016/j.lfs.2018.10.050

Cited by 19 publications

(12 citation statements)

References 36 publications

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“…The most upregulated pathway in K562/ADM cells was the PI3K/AKT signaling pathway, which was related to the reprogramming of glucose metabolism and the occurrence of MDR. The PI3K/AKT pathway was upregulated in cancer cells, which may lead to aerobic glycolysis and MDR enhancement 31 . The increased expression of GLUT4 confirmed the excessive activation of the PI3K/AKT/mTOR signaling pathway in cancer cells, which may enhance the ability of MDR cells to rapidly transport and consume glucose via glycolysis to produce ATP.…”

Section: Bcrpmentioning

confidence: 99%

“…Previous studies showed that the PI3K/AKT pathway enhanced the biological basis of cancer by effectively expressing ABC transporters containing p-glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2), whose activation may reduce the response to chemotherapy drugs and enhance the drug efflux 29,30 . Due to the acidified micro-environment in tumor cells, aerobic glycolysis may confer MDR to cancer cells, which may reduce drug absorption and efficiency, and/or increase the content of intermediate metabolites 31,32 . Reducing the cellular energy of glycolytic metabolism may reduce drug resistance by reducing the outflow of drugs from cells.…”

Section: Introductionmentioning

confidence: 99%

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PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers

et al. 2020

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Multidrug resistance (MDR) is the dominant challenge in the failure of chemotherapy in cancers. Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that spreads intracellular signal cascades and regulates a variety of cellular processes. PI3Ks are considered significant causes of chemoresistance in cancer therapy. Protein kinase B (AKT) is also a significant downstream effecter of PI3K signaling, and it modulates several pathways, including inhibition of apoptosis, stimulation of cell growth, and modulation of cellular metabolism. This review highlights the aberrant activation of PI3K/AKT as a key link that modulates MDR. We summarize the regulation of numerous major targets correlated with the PI3K/AKT pathway, which is further related to MDR, including the expression of apoptosis-related protein, ABC transport and glycogen synthase kinase-3 beta (GSK-3β), synergism with nuclear factor kappa beta (NF-κB) and mammalian target of rapamycin (mTOR), and the regulation of glycolysis.

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Section: Bcrpmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers

et al. 2020

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“…Shinohara et al reported that mTOR mediates the expression regulation by Bcr-Abl of the balance between the two pyruvate kinase (PKM) isoforms 1 and 2 [84]; this glycolytic kinase is crucial in the control of glucose fate, between aerobic glycolysis and OXPHOS [85]. Finally, a sustained activity of the PI3K/Akt/mTOR signaling module has been reported to participate in the glycolytic phenotype of adriamycin-resistant CML cells [86].…”

Section: Chronic Myeloid Leukemiamentioning

confidence: 99%

mTOR Regulation of Metabolism in Hematologic Malignancies

Mirabilii

Ricciardi

Tafuri

2020

Cells

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Neoplastic cells rewire their metabolism, acquiring a selective advantage over normal cells and a protection from therapeutic agents. The mammalian Target of Rapamycin (mTOR) is a serine/threonine kinase involved in a variety of cellular activities, including the control of metabolic processes. mTOR is hyperactivated in a large number of tumor types, and among them, in many hematologic malignancies. In this article, we summarized the evidence from the literature that describes a central role for mTOR in the acquisition of new metabolic phenotypes for different hematologic malignancies, in concert with other metabolic modulators (AMPK, HIF1α) and microenvironmental stimuli, and shows how these features can be targeted for therapeutic purposes.

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“…Lactate dehydrogenase (LDH), as the essential enzyme for shifting pyruvate to lactate to produce ATP, is of primary importance in glucose metabolism. Zhang et al reported that the high aerobic glycolysis flux decreased the chemosensitivity of leukemia to adriamycin, which was regulated by the AKT-mTOR pathway and could be reversed by the LDH inhibitor oxamate [37]. As one of the frequently used chemotherapeutic drugs for prostate cancer, the resistance of docetaxel was revealed to be regulated by L-lactate dehydrogenase A (LDHA)-mediated lactate homeostasis [38].…”

Section: Glucose and Energy Metabolismmentioning

confidence: 99%

Targeting Cancer Metabolism to Resensitize Chemotherapy: Potential Development of Cancer Chemosensitizers from Traditional Chinese Medicines

Guo

Tan

Chen

et al. 2020

Cancers

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Cancer is a common and complex disease with high incidence and mortality rates, which causes a severe public health problem worldwide. As one of the standard therapeutic approaches for cancer therapy, the prognosis and outcome of chemotherapy are still far from satisfactory due to the severe side effects and increasingly acquired resistance. The development of novel and effective treatment strategies to overcome chemoresistance is urgent for cancer therapy. Metabolic reprogramming is one of the hallmarks of cancer. Cancer cells could rewire metabolic pathways to facilitate tumorigenesis, tumor progression, and metastasis, as well as chemoresistance. The metabolic reprogramming may serve as a promising therapeutic strategy and rekindle the research enthusiasm for overcoming chemoresistance. This review focuses on emerging mechanisms underlying rewired metabolic pathways for cancer chemoresistance in terms of glucose and energy, lipid, amino acid, and nucleotide metabolisms, as well as other related metabolisms. In particular, we highlight the potential of traditional Chinese medicine as a chemosensitizer for cancer chemotherapy from the metabolic perspective. The perspectives of metabolic targeting to chemoresistance are also discussed. In conclusion, the elucidation of the underlying metabolic reprogramming mechanisms by which cancer cells develop chemoresistance and traditional Chinese medicines resensitize chemotherapy would provide us a new insight into developing promising therapeutics and scientific evidence for clinical use of traditional Chinese medicine as a chemosensitizer for cancer therapy.

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Targeting glycometabolic reprogramming to restore the sensitivity of leukemia drug-resistant K562/ADM cells to adriamycin

Cited by 19 publications

References 36 publications

PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers

PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers

mTOR Regulation of Metabolism in Hematologic Malignancies

Targeting Cancer Metabolism to Resensitize Chemotherapy: Potential Development of Cancer Chemosensitizers from Traditional Chinese Medicines

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