Nrf2 signaling pathway in cisplatin chemotherapy: Potential involvement in organ protection and chemoresistance

Mirzaei, Sepideh; Mohammadi, Aliasghar Tabatabaei; Gholami, Milad; Hashemi, Farid; Zarrabi, Ali; Zabolian, Amirhossein; Hushmandi, Kiavash; Makvandi, Pooyan; Samec, Marek; Líšková, Alena; Kubatka, Peter; Nabavi, Noushin; Aref, Amir Reza; Ashrafizadeh, Milad; Khan, Haroon; Najafi, Masoud

doi:10.1016/j.phrs.2021.105575

Cited by 113 publications

(55 citation statements)

References 265 publications

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“…Cisplatin (CP) is a platinumcontaining drug that was first discovered in 1965 and became famous due to its great antimicrobial activity. More experiments demonstrated that platinum-containing agents can possess anti-cancer activity [8][9][10][11][12][13]. As an electrophilic reagent, platinum can interact with nucleophilic residues of nucleobases, including guanine and adenosine by forming covalent bonds.…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…In particular, it has been documented that GULP1 activates SMAD3 [ 27 ] or inactivates AKT/PDK1 and MAPK [ 28 ] in ovarian cancer cells, while it inhibits the nuclear translocation of NRF2 and subsequently reduces the expression of HMOX1 in bladder cancer cells [ 29 ]. Interestingly, all of these potentially downstream of GULP1 have been linked to CDDP resistance [ 10 , 24 , 32 , 33 , 34 , 35 ]. Further studies are required for elucidating the molecular mechanisms responsible for AR/GULP1-mediated chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer

Teramoto

Jiang

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et al. 2021

IJMS

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The underlying molecular mechanisms of resistance to cisplatin-based systemic chemotherapy in bladder cancer patients remain to be elucidated, while the link between androgen receptor (AR) activity and chemosensitivity in urothelial cancer has been implicated. Our DNA microarray analysis in control vs. AR knockdown bladder cancer lines identified GULP1 as a potential target of AR signaling. We herein determined the relationship between AR activity and GULP1 expression in bladder cancer cells and then assessed the functional role of GULP1 in cisplatin sensitivity. Androgen treatment in AR-positive cells or AR overexpression in AR-negative cells considerably reduced the levels of GULP1 expression. Chromatin immunoprecipitation further showed direct interaction of AR with the promoter region of GULP1. Meanwhile, GULP1 knockdown sublines were significantly more resistant to cisplatin treatment compared with respective controls. GULP1 knockdown also resulted in a significant decrease in apoptosis, as well as a significant increase in G2/M phases, when treated with cisplatin. In addition, GULP1 was immunoreactive in 74% of muscle-invasive bladder cancers from patients who had subsequently undergone neoadjuvant chemotherapy, including 53% of responders showing moderate (2+)/strong (3+) expression vs. 23% of non-responders showing 2+/3+ expression (P = 0.044). These findings indicate that GULP1 represents a key downstream effector of AR signaling in enhancing sensitivity to cisplatin treatment.

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“…Methylation of the promoter region of miR-338-5p-5p can also lead to low levels of miR-338-5p-5p in astrocytoma. The miRNA is an important type of small molecule non-coding RNA, which can not only be used as an anti-tumor treatment strategy (for example, in this study, the entire sequence of hsa-pre-miR-338-5p was prepared as rotavirus/lentivirus), but also the deficiency of miRs would be the possible mechanisms for the aberrant expression of its target gene (some pro-oncogene) in malignant tumor tissues (26,(52)(53)(54). In terms of molecular mechanism, miRNA is used in the 3'UTR region of its target gene through a sequence-specific mechanism (55)(56)(57)(58)(59).…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

et al. 2021

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The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.

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Nrf2 signaling pathway in cisplatin chemotherapy: Potential involvement in organ protection and chemoresistance

Cited by 113 publications

References 265 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

Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

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