TXNIP induces growth arrest and enhances ABT263‐induced apoptosis in mixed‐lineage leukemia‐rearranged acute myeloid leukemia cells

Noura, Mina; Matsuo, Hidemasa; Koyama, Akihiro; Adachi, Souichi; Masutani, Hiroshi

doi:10.1002/2211-5463.12908

Cited by 12 publications

(5 citation statements)

References 42 publications

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“…TXNIP was originally found as a target of vitamin D in HL60 cells and shown to inhibit the antioxidant activity of thioredoxin [40]. It is noteworthy that TXNIP overexpression significantly suppressed the proliferation of two acute myeloid leukemia cell lines, i.e., MOLM-13 and MV4-11 [41]. On these bases, we hypothesize that TXNIP upregulation might play a role in retarding HL60-R proliferation.…”

Section: Discussionmentioning

confidence: 84%

A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms

Locatelli

Cazzaniga

Fedele

et al. 2021

CIMB

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Chemoresistance causes cancer relapse and metastasis, thus remaining the major obstacle to cancer therapy. While some light has been shed on the underlying mechanisms, it is clear that chemoresistance is a multifaceted problem strictly interconnected with the high heterogeneity of neoplastic cells. We utilized two different human cell lines, i.e., LoVo colon cancer and promyelocytic leukemia HL60 cells sensitive and resistant to doxorubicin (DXR), largely used as a chemotherapeutic and frequently leading to chemoresistance. LoVo and HL60 resistant cells accumulate less reactive oxygen species by differently modulating the levels of some pro- and antioxidant proteins. Moreover, the content of intracellular magnesium, known to contribute to protect cells from oxidative stress, is increased in DXR-resistant LoVo through the upregulation of MagT1 and in DXR-resistant HL60 because of the overexpression of TRPM7. In addition, while no major differences in mitochondrial mass are observed in resistant HL60 and LoVo cells, fragmented mitochondria due to increased fission and decreased fusion are detected only in resistant LoVo cells. We conclude that DXR-resistant cells evolve adaptive mechanisms to survive DXR cytotoxicity by activating different molecular pathways.

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Section: Discussionmentioning

confidence: 84%

A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms

Locatelli

Cazzaniga

Fedele

et al. 2021

CIMB

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“…Poor survival is correlated with a lower expression of TXNIP in acute myeloid leukemia. [162] The human histiocytic/monocytic leukemia cells have several-fold higher TRXR expression compared to non-transformed cells. Both normal and transformed cells were found to secrete TRXR.…”

Section: Tumor Typementioning

confidence: 99%

“…Indeed, it is common for various types of cancers to downregulate TXNIP [ 159 , 160 ]. The TXNIP was suggested to be used as a prognostic marker as its expression inversely correlates with the pathological grade of tumor [ 142 , 161 ], while its overexpression can indicate a longer survival of cancer patients [ 156 , 162 , 163 , 164 ]. Among the TXNDC protein family, TXNDC5 has been studied the most and was found to be overexpressed in tumor tissues [ 165 , 166 , 167 ], and its high expression correlates with poor survival [ 168 ].…”

Section: Redox Homeostasismentioning

confidence: 99%

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

et al. 2020

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Cancer remains an elusive, highly complex disease and a global burden. Constant change by acquired mutations and metabolic reprogramming contribute to the high inter- and intratumor heterogeneity of malignant cells, their selective growth advantage, and their resistance to anticancer therapies. In the modern era of integrative biomedicine, realizing that a personalized approach could benefit therapy treatments and patients’ prognosis, we should focus on cancer-driving advantageous modifications. Namely, reactive oxygen species (ROS), known to act as regulators of cellular metabolism and growth, exhibit both negative and positive activities, as do antioxidants with potential anticancer effects. Such complexity of oxidative homeostasis is sometimes overseen in the case of studies evaluating the effects of potential anticancer antioxidants. While cancer cells often produce more ROS due to their increased growth-favoring demands, numerous conventional anticancer therapies exploit this feature to ensure selective cancer cell death triggered by excessive ROS levels, also causing serious side effects. The activation of the cellular NRF2 (nuclear factor erythroid 2 like 2) pathway and induction of cytoprotective genes accompanies an increase in ROS levels. A plethora of specific targets, including those involved in thioredoxin (TRX) and glutathione (GSH) systems, are activated by NRF2. In this paper, we briefly review preclinical research findings on the interrelated roles of the NRF2 pathway and TRX and GSH systems, with focus given to clinical findings and their relevance in carcinogenesis and anticancer treatments.

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“…Aside from the expression regulation, TXNIP is another line of Trx activity control, acting as an inhibitor of Trx ( Patwari et al, 2006 ). TXNIP is a tumor suppressor, commonly silenced in cancer cells, by genetic or epigenetic events ( Morrison et al, 2014 ; Zhang P. et al, 2017 ; Noura et al, 2020 ).…”

Section: Significance Of Trx System In Redox Balance Maintenancementioning

confidence: 99%

The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance

Jovanović

Podolski-Renić

Krasavin

et al. 2022

Front. Mol. Biosci.

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The intracellular redox homeostasis is a dynamic balancing system between the levels of free radical species and antioxidant enzymes and small molecules at the core of cellular defense mechanisms. The thioredoxin (Trx) system is an important detoxification system regulating the redox milieu. This system is one of the key regulators of cells’ proliferative potential as well, through the reduction of key proteins. Increased oxidative stress characterizes highly proliferative, metabolically hyperactive cancer cells, which are forced to mobilize antioxidant enzymes to balance the increase in free radical concentration and prevent irreversible damage and cell death. Components of the Trx system are involved in high-rate proliferation and activation of pro-survival mechanisms in cancer cells, particularly those facing increased oxidative stress. This review addresses the importance of the targetable redox-regulating Trx system in tumor progression, as well as in detoxification and protection of cancer cells from oxidative stress and drug-induced cytotoxicity. It also discusses the cancer cells’ counteracting mechanisms to the Trx system inhibition and presents several inhibitors of the Trx system as prospective candidates for cytostatics’ adjuvants. This manuscript further emphasizes the importance of developing novel multitarget therapies encompassing the Trx system inhibition to overcome cancer treatment limitations.

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TXNIP induces growth arrest and enhances ABT263‐induced apoptosis in mixed‐lineage leukemia‐rearranged acute myeloid leukemia cells

Cited by 12 publications

References 42 publications

A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms

A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance

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