Knockout of PRDX6 induces mitochondrial dysfunction and cell cycle arrest at G2/M in HepG2 hepatocarcinoma cells

López-Grueso, María José; Lagal, Daniel J.; García-Jiménez, Álvaro Fernando; Tarradas, Rosa María; Carmona‐Hidalgo, Beatriz; Peinado, J.; Requejo-Aguilar, Raquel; Bárcena, José Antonio; Padilla, C. Alicia

doi:10.1016/j.redox.2020.101737

Cited by 49 publications

(42 citation statements)

References 80 publications

(101 reference statements)

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“…22 Additionally, Increasing number of studies have found that PRDXs affect the prognosis of patients with various types of tumors, including breast, liver, ovarian, and gastric cancers. [23][24][25][26] PRDX1, PRDX2, and PRDX6 have also been reported to be highly expressed in OSCC. [27][28][29] To date, few studies have investigated the relationship between the PRDX family and metastasis and prognosis of OSCC.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Potential Prognostic Value of Peroxiredoxin 1 in Oral Squamous Cell Carcinoma

Shen¹,

Xu²,

Li³

et al. 2021

CMAR

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The role of the peroxiredoxin (PRDX) family in oral squamous cell carcinoma (OSCC) remains unclear. This study aimed to investigate the expression of PRDXs and their effects on the prognosis in OSCC. Methods: The expression of PRDXs and their effects on prognosis were analysed in 216 OSCC samples from The Cancer Genome Atlas (TCGA) database. OSCC tissues and adjacent noncancerous tissues (ANTs) were obtained from 68 clinical patients. Quantitative real-time (qRT)-PCR, Western blot, and immunohistochemical (IHC) staining were used to verify the relationship between the expression level of PRDX1 and different clinical features. Gene set enrichment analysis (GSEA) was used to examine the molecular mechanism of PRDX1 in OSCC. Results: PRDX1 was found to be the only gene in PRDX family that highly expressed in OSCC samples and affected the prognosis of patients with OSCC. PRDX1 expression was significantly related to tumor stage, lymphatic metastasis, and pathological grade. A nomogram consisting of tumor stage, N stage, and PRDX1 level was constructed. GSEA showed that high expression of PRDX1 involved many cancer-related molecular functions and signaling pathways. Conclusion: PRDX1 may play an important role in the occurrence and development of OSCC, and may be a potential new target for OSCC treatment.

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Section: Introductionmentioning

confidence: 99%

Assessment of Potential Prognostic Value of Peroxiredoxin 1 in Oral Squamous Cell Carcinoma

Shen¹,

Xu²,

Li³

et al. 2021

CMAR

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show abstract

“…There had been reported that inhibition or deficiency of PRDX6 could increase the intracellular oxidative stress and cause the cell injury [ [39] , [40] , [41] ]. Increasing evidence had demonstrated that PRDX6 had a critical role in the development of human cancers [ 19 , 23 ]. High levels of PRDX6 has been found in multiple cancer cells and contributes to the proliferation of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…In the reported study [ 23 ], knockout of PRDX6 by CRISPR/Cas9 system had an antiproliferative effect in tumor cells. In the present study, we also screened the viable cell which had the deletion of PRDX6 by CRISPR/Cas9 system.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, there have been reported that overexpressed PRDX6 could facilitate resistance to radiation and chemotherapeutics, while the inhibition of PRDX6 can sensitize cells to chemotherapy and promote apoptosis [ 16 , 21 , 22 ]. Conversely, the deficiency or downregulation of PRDX6 promoted the cell cycle arrest and apoptosis of cancer cells [ 17 , 23 ]. Thus, targeted inhibition of PRDX6 provides a potential therapeutic strategy for cancers with high expression of PRDX6.…”

Section: Introductionmentioning

confidence: 99%

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Identification of peroxiredoxin 6 as a direct target of withangulatin A by quantitative chemical proteomics in non-small cell lung cancer

et al. 2021

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Peroxiredoxin 6 (PRDX6), as a bifunctional enzyme with glutathione peroxidase activity (GPx) and Ca2 + -independent phospholipase A2 (iPLA2) activity, has a higher expression in various cancer cells, which leads to the increase of antioxidant properties and promotes tumorigenesis. However, only a few inhibitors of PRDX6 have been discovered to date, especially the covalent inhibitors of PRDX6. Here, we firstly identified Withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PRDX6. SILAC-ABPP identified that WA could directly bind to PRDX6 and inactivate the enzyme activity of PRDX6 by the α, β-unsaturated ketone moiety. Moreover, WA also facilitated the generation of ROS, and inhibited the GPx and iPLA2 activities. However, WA-1, with a reduced α, β-unsaturated ketone moiety, had no significant inhibition of the GPx and iPLA2 activities. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selectively covalent binding of WA to the cysteine 47 residue (Cys47) of PRDX6, while mutation of Cys47 blocked the binding of WA to PRDX6. Notably, WA-mediated cytotoxicity and inhibition of the GPx and iPLA2 activities were almost abolished by the deficiency of PRDX6. Therefore, this study indicates that WA is a novel PRDX6 covalent inhibitor, which could covalently bind to the Cys47 of PRDX6 and holds great potential in developing anti-tumor agents for targeting PRDX6.

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“…Previous reports have pointed out that mitochondrial dysfunction has been linked to cancer metastasis (156). During the process of TGF-b1 induced EMT, mitochondria will be damaged.…”

Section: Lung Cancermentioning

confidence: 99%

Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors

et al. 2021

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Epithelial-to-mesenchymal transition (EMT), a complicated program through which polarized epithelial cells acquire motile mesothelial traits, is regulated by tumor microenvironment. EMT is involved in tumor progression, invasion and metastasis via reconstructing the cytoskeleton and degrading the tumor basement membrane. Accumulating evidence shows that resveratrol, as a non-flavonoid polyphenol, can reverse EMT and inhibit invasion and migration of human tumors via diverse mechanisms and signaling pathways. In the present review, we will summarize the detailed mechanisms and pathways by which resveratrol and its analogs (e.g. Triacetyl resveratrol, 3,5,4’-Trimethoxystilbene) might regulate the EMT process in cancer cells to better understand their potential as novel anti-tumor agents. Resveratrol can also reverse chemoresistance via EMT inhibition and improvement of the antiproliferative effects of conventional treatments. Therefore, resveratrol and its analogs have the potential to become novel adjunctive agents to inhibit cancer metastasis, which might be partly related to their blocking of the EMT process.

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Knockout of PRDX6 induces mitochondrial dysfunction and cell cycle arrest at G2/M in HepG2 hepatocarcinoma cells

Cited by 49 publications

References 80 publications

Assessment of Potential Prognostic Value of Peroxiredoxin 1 in Oral Squamous Cell Carcinoma

Assessment of Potential Prognostic Value of Peroxiredoxin 1 in Oral Squamous Cell Carcinoma

Identification of peroxiredoxin 6 as a direct target of withangulatin A by quantitative chemical proteomics in non-small cell lung cancer

Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors

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