FoxM1-dependent and fatty acid oxidation-mediated ROS modulation is a cell-intrinsic drug resistance mechanism in cancer stem-like cells

Choi, Hae-Ji; Jhe, Yoo-Lim; Kim, Jungmin; Lim, Ju Yeon; Lee, Jae Eun; Shin, Min-Kyue; Cheong, Jae‐Ho

doi:10.1016/j.redox.2020.101589

Cited by 66 publications

(53 citation statements)

References 32 publications

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“…ROS overgeneration leads to mitochondrial injury and provides the conditions for mitophagy, resulting in a decrease in cancer cell viability [74]. Noteably, in respect to the role of ROS in reducing cancer cell viability, it has been reported that cancer stem cells (CSCs) preserve ROS generation at low levels to obtain chemoresistance [75]. Therefore, using agents that enhance ROS generation is improtant in providing chemosensitivity.…”

Section: Ros Role In Cancermentioning

confidence: 99%

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

et al. 2021

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The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.

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Section: Ros Role In Cancermentioning

confidence: 99%

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

et al. 2021

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“…The glutaminase inhibitors BPTES and CB839 strongly inhibit the growth of glutamine-addicted tumors even when used alone, but they have been shown to be more potent when combined with other metabolic inhibitors or conventional chemotherapy [ 68 , 69 , 70 , 171 , 178 , 179 ]. The FAO inhibitor etomoxir also enhanced the therapeutic effect of conventional chemotherapy in several types of cancers in vivo [ 138 , 180 , 181 ]. The selective Nrf2 inhibitor trigonelline, the xCT inhibitor sulfasalazine, the GSH inhibitor buthionine sulfoximine, and the Trx inhibitor auranofin induce cell death by accumulating ROS in CSCs.…”

Section: Therapeutic Strategies For Targeting Csc Metabolismmentioning

confidence: 99%

The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells

Tanabe

Sahara

2020

Cancers

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Numerous findings have indicated that CSCs, which are present at a low frequency inside primary tumors, are the main cause of therapy resistance and cancer recurrence. Although various therapeutic methods targeting CSCs have been attempted for eliminating cancer cells completely, the complicated characteristics of CSCs have hampered such attempts. In analyzing the biological properties of CSCs, it was revealed that CSCs have a peculiar metabolism that is distinct from non-CSCs to maintain their stemness properties. The CSC metabolism involves not only the catabolic and anabolic pathways, but also intracellular signaling, gene expression, and redox balance. In addition, CSCs can reprogram their metabolism to flexibly respond to environmental changes. In this review, we focus on the flexible metabolic mechanisms of CSCs, and highlight the new therapeutics that target CSC metabolism.

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“…Furthermore, downregulation of OXPHOS via SIRT1/PGC1-α knockdown resensitizes cancer cells, suggesting that OXPHOS inhibition may represent an attractive addition to adjuvant chemotherapy. Despite mitochondrial function being high in these studies, ROS levels are significantly lower in CSCs [ 53 ], which also explains their more powerful antioxidant defense system compared with bulk tumors. A strong quenching process keeps ROS levels low, and helps in the maintenance of the stemness of CSCs, thereby contributing to therapy resistance [ 54 ].…”

Section: Unique Features Of Cscsmentioning

confidence: 99%

Role of Mitochondria-Cytoskeleton Interactions in the Regulation of Mitochondrial Structure and Function in Cancer Stem Cells

Kim

Cheong

2020

Cells

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Despite the promise of cancer medicine, major challenges currently confronting the treatment of cancer patients include chemoresistance and recurrence. The existence of subpopulations of cancer cells, known as cancer stem cells (CSCs), contributes to the failure of cancer therapies and is associated with poor clinical outcomes. Of note, one of the recently characterized features of CSCs is augmented mitochondrial function. The cytoskeleton network is essential in regulating mitochondrial morphology and rearrangement, which are inextricably linked to its functions, such as oxidative phosphorylation (OXPHOS). The interaction between the cytoskeleton and mitochondria can enable CSCs to adapt to challenging conditions, such as a lack of energy sources, and to maintain their stemness. Cytoskeleton-mediated mitochondrial trafficking and relocating to the high energy requirement region are crucial steps in epithelial-to-mesenchymal transition (EMT). In addition, the cytoskeleton itself interplays with and blocks the voltage-dependent anion channel (VDAC) to directly regulate bioenergetics. In this review, we describe the regulation of cellular bioenergetics in CSCs, focusing on the cytoskeleton-mediated dynamic control of mitochondrial structure and function.

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FoxM1-dependent and fatty acid oxidation-mediated ROS modulation is a cell-intrinsic drug resistance mechanism in cancer stem-like cells

Cited by 66 publications

References 32 publications

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells

Role of Mitochondria-Cytoskeleton Interactions in the Regulation of Mitochondrial Structure and Function in Cancer Stem Cells

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