The Warburg effect on radioresistance: Survival beyond growth

Kang, Hyunkoo; Kim, Byeongsoo; Park, Junhyeong; Youn, HyeSook; Youn, BuHyun

doi:10.1016/j.bbcan.2023.188988

Cited by 17 publications

(4 citation statements)

References 155 publications

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“…The Warburg effect results in the rapid production of high levels of ATP and thus the necessary materials for biosynthesis in cancer cells. Subsequently, the absence of the Warburg effect may harm several aspects of cancer cells besides ATP production, such as biosynthesis of multiple components, redox homeostasis and DNA damage repair ( 32 ). In the present study, it was found that the proliferation of A498 and OSRC2 cells was significantly downregulated following the knockdown of KMT5C expression.…”

Section: Resultsmentioning

confidence: 99%

Lysine methyltransferase 5C increases the proliferation and metastatic abilities of clear cell renal cell carcinoma via aerobic glycolysis

Zeng,

Wan,

Chang

et al. 2024

Int J Oncol

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Among all types of renal cancer, clear cell renal cell carcinoma (ccRCC) is the most common and lethal subtype and is associated with a high risk of metastasis and recurrence. Histone modifications regulate several biological processes that are fundamental to the development of cancer. Lysine methyltransferase 5C (KMT5C; also known as SUV420H2) is an epigenetic modifier responsible for the trimethylation of H4K20, which drives critical cellular events, including genome integrity, cell growth and epithelial-mesenchymal transition (EMT), in various types of cancer. However, the role of KMT5C in ccRCC remains unclear. As such, the expression and function of KMT5C in ccRCC were investigated in the present study. KMT5C expression was significantly increased in ccRCC tissues compared with normal tissues (P<0.0001), and it was closely associated with the overall survival rate of patients with ccRCC. By establishing ccRCC cell lines with KMT5C expression knockdown, the role of KMT5C in the maintenance of aerobic glycolysis in ccRCC cells via the regulation of several vital glycolytic genes was identified. Additionally, KMT5C promoted the proliferation and EMT of ccRCC cells by controlling crucial EMT transcriptional factors. Together, these data suggested that KMT5C may act as an oncoprotein, guide molecular diagnosis, and shed light on novel drug development and therapeutic strategies for patients with ccRCC.

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Section: Resultsmentioning

confidence: 99%

Lysine methyltransferase 5C increases the proliferation and metastatic abilities of clear cell renal cell carcinoma via aerobic glycolysis

Zeng,

Wan,

Chang

et al. 2024

Int J Oncol

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“…However, this metabolic process is not constant. In previous studies, tumor cells still preferentially use glycolysis to produce lactic acid for energy under normal oxidation conditions rather than OXPHOS through aerobic respiration, a process known as the Warburg effect [68,69]. Similar to the "aerobic glycolysis" of tumor cells, the chemotaxis, phagocytosis, and proliferation of microglia after being activated into M1 type require dynamic recombination of the actin cytoskeleton and secretion of cytokines, so that M1 type microglia are in a state of energy deficiency.…”

Section: The Immunometabolism Of Microglia In Drmentioning

confidence: 99%

Redox Regulation of Immunometabolism in Microglia Underpinning Diabetic Retinopathy

Cai,

Xia,

Zhang

2024

Antioxidants

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Diabetic retinopathy (DR) is the leading cause of visual impairment and blindness among the working-age population. Microglia, resident immune cells in the retina, are recognized as crucial drivers in the DR process. Microglia activation is a tightly regulated immunometabolic process. In the early stages of DR, the M1 phenotype commonly shifts from oxidative phosphorylation to aerobic glycolysis for energy production. Emerging evidence suggests that microglia in DR not only engage specific metabolic pathways but also rearrange their oxidation-reduction (redox) system. This redox adaptation supports metabolic reprogramming and offers potential therapeutic strategies using antioxidants. Here, we provide an overview of recent insights into the involvement of reactive oxygen species and the distinct roles played by key cellular antioxidant pathways, including the NADPH oxidase 2 system, which promotes glycolysis via enhanced glucose transporter 4 translocation to the cell membrane through the AKT/mTOR pathway, as well as the involvement of the thioredoxin and nuclear factor E2-related factor 2 antioxidant systems, which maintain microglia in an anti-inflammatory state. Therefore, we highlight the potential for targeting the modulation of microglial redox metabolism to offer new concepts for DR treatment.

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“…Radiation therapy (RT) is widely acknowledged as one of the most effective non-surgical methods for managing malignant tumors; however, its efficacy is impeded by various adverse effects that affect multiple organs (including the skin), damage to healthy tissues caused by radiation, and the development of significant radioresistance in cancer cells [3,4]. Multiple processes are associated with the development of radioresistance, such as epigenetic modifications and the activation of survival signaling pathways [5]. However, research has shown that curcumin can enhance the radiosensitivity of cancer cells, making them more susceptible to the effects of ionizing radiation, and in so doing increase cytotoxicity [6].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity Enhancement in Osteosarcoma with Multifunctional I-131 Radiotherapeutic Nanoparticles: In Vitro Three-Dimensional Spheroid Model and Release Kinetics Modeling

Marshall,

Taweesap,

Saelim

et al. 2024

Molecules

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This novel radiolabeled chitosan nanoparticle, facilitated with curcumin, increased doxorubicin cytotoxicity and radiosensitivity to MG-63 osteosarcoma cells in a three-dimensional model. Delivery of the anti-epidermal growth factor receptor (EGFR) targeted carboxymethyl chitosan nanoparticles, directly labeled with Na131I (ICED-N), achieved deep tumor penetration in a three-dimensional model. Of three kinetic models, the Higuchi model more closely matched the experimental curve and release profiles. The anti-EGFR targeting resulted in a 513-fold greater targeting efficacy to MG-63 (EGFR+) cells than the control fibroblast (EGFR−) cells. The curcumin-enhanced ICED-N (4 × 0.925 MBq) fractionated-dose regime achieved an 18.3-fold increase in cell cytotoxicity compared to the single-dose (1 × 3.70 MBq) doxorubicin-loaded nanoparticle, and a 13.6-fold increase in cell cytotoxicity compared to the single-dose Na131I nanoparticle. Moreover, the ICED-N fractionated dose increased cells in the G2/M phase 8.78-fold, indicating the cell cycle arrest in the G2/M phase is associated with DNA fragmentation, and the intracellular damage is unable to be repaired. Overall, the results indicate that the fractionated dose was more efficacious than a single dose, and curcumin substantially increased doxorubicin cytotoxicity and amplified osteosarcoma cell radiosensitivity to Na131I.

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The Warburg effect on radioresistance: Survival beyond growth

Cited by 17 publications

References 155 publications

Lysine methyltransferase 5C increases the proliferation and metastatic abilities of clear cell renal cell carcinoma via aerobic glycolysis

Lysine methyltransferase 5C increases the proliferation and metastatic abilities of clear cell renal cell carcinoma via aerobic glycolysis

Redox Regulation of Immunometabolism in Microglia Underpinning Diabetic Retinopathy

Cytotoxicity Enhancement in Osteosarcoma with Multifunctional I-131 Radiotherapeutic Nanoparticles: In Vitro Three-Dimensional Spheroid Model and Release Kinetics Modeling

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