p53 protects lung cancer cells against metabolic stress

Sinthupibulyakit, Chompunoot; Ittarat, Wanida; Clair, William H. St.; Clair, Daret K. St.

doi:10.3892/ijo_00000811

Cited by 24 publications

(10 citation statements)

References 32 publications

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“…We speculated that 2-DG may inhibit glycolysis in LCSCs and induce a reliance on mitochondrial OXPHOS for energy supply and stemness maintenance. Consistent with our findings, a publication showed that 2-DG can increase OXPHOS and ROS levels in lung cancer cells [14][15][16]. To provide support for this hypothesis, we examined and compared the changes in OXPHOS after treatment with 2-DG.…”

Section: -Dg Increases Liver Cancer Stem Cell Stemness By Upregulatisupporting

confidence: 87%

Increased Oxidative Phosphorylation Is Required for Stemness Maintenance in Liver Cancer Stem Cells from Hepatocellular Carcinoma Cell Line HCCLM3 Cells

Liu

Luo

et al. 2020

IJMS

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Cancer stem cells (CSCs) are considered to be the main cause of tumor recurrence, metastasis, and an unfavorable prognosis. Energy metabolism is closely associated with cell stemness. However, how the stemness of liver cancer stem cells (LCSCs) is regulated by metabolic/oxidative stress remains poorly understood. In this study, we compare the metabolic differences between LCSCs and the hepatocellular carcinoma cell line HCCLM3, and explore the relationship between metabolism and LCSC stemness. We found that LCSCs from the hepatocellular carcinoma cell HCCLM3 exhibited more robust glucose metabolism than HCCLM3, including glycolysis, oxidative phosphorylation (OXPHOS), and pyruvate produced by glycolysis entering mitochondria for OXPHOS. Moreover, 2-deoxy-D-glucose (2-DG) enhanced the LCSC stemness by upregulating OXPHOS. In contrast, Mdivi-1 reduced the levels of OXPHOS and weakened the stemness by inhibiting mitochondrial fission. Together, our findings clarify the relationship between energy metabolism and LCSC stemness and may provide theoretical guidance and potential therapeutic approaches for liver cancer.

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Section: -Dg Increases Liver Cancer Stem Cell Stemness By Upregulatisupporting

confidence: 87%

Increased Oxidative Phosphorylation Is Required for Stemness Maintenance in Liver Cancer Stem Cells from Hepatocellular Carcinoma Cell Line HCCLM3 Cells

Liu

Luo

et al. 2020

IJMS

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“…In this respect, it was shown that the cytotoxic effect of 2-deoxyglucose (2-DG) on A549 lung cancer cells depended on inactivation of mitochondria in p53 −/− cells. The observation that the Warburg effect was only evidenced in cells in which mitochondria were impaired supported the idea of a functional link between glycolysis and the oxidative reactions of the organelle [ 61 ]. Furthermore, the often quoted idea that in cancer cells the mitochondria stop respiring in order to save carbon skeletons for the biosynthesis of other biomolecules required for rapid growth is not compatible with the observation that tumors actually excrete high amounts of lactate [ 62 ].…”

Section: Ros and Cancermentioning

confidence: 83%

Energy and Redox Homeostasis in Tumor Cells

Oliveira

Amoêdo

Rumjanek

2012

International Journal of Cell Biology

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Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1). The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg's original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.

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“…Sinthupibulyakit et al . reported that the glucose analog 2-DG increases mtROS levels in lung cancer cells [ 35 ]. Our cell viability experiments showed that QBC939 cells had the similar sensitivity in 2-DG with HepG2 cells, and that the levels of overall ROS and mtROS were increased ( Fig 4A–4D ).…”

Section: Discussionmentioning

confidence: 99%

Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS

Sheng

Shen

et al. 2017

PLoS ONE

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The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells. It is suggested that there are some differences in the metabolism of glucose in hepatocellular carcinoma and cholangiocarcinoma cells, and the activation of PPP pathway may be related to the drug resistance. Through the detection of autophagy substrates p62 and LC3, found that QBC939 cells have a higher flow of autophagy, autophagy inhibitor chloroquine can significantly increase the sensitivity of cisplatin in cholangiocarcinoma cells compared with hepatocellular carcinoma HepG2 cells. The mechanism may be related to the inhibition of QBC939 cells with higher activity of the PPP, the key enzyme G6PDH, which reduces the antioxidant capacity of cells and increases intracellular ROS, especially mitochondrial ROS. Therefore, we hypothesized that autophagy and the oxidative stress resistance mediated by glucose metabolism may be one of the causes of cisplatin resistance in cholangiocarcinoma cells. It is suggested that according to the metabolism characteristics of tumor cells, inhibition of autophagy lysosome pathway with chloroquine may be a new route for therapeutic agents against cholangiocarcinoma.

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p53 protects lung cancer cells against metabolic stress

Cited by 24 publications

References 32 publications

Increased Oxidative Phosphorylation Is Required for Stemness Maintenance in Liver Cancer Stem Cells from Hepatocellular Carcinoma Cell Line HCCLM3 Cells

Increased Oxidative Phosphorylation Is Required for Stemness Maintenance in Liver Cancer Stem Cells from Hepatocellular Carcinoma Cell Line HCCLM3 Cells

Energy and Redox Homeostasis in Tumor Cells

Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS

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