Identification of simvastatin-regulated targets associated with JNK activation in DU145 human prostate cancer cell death signaling

Jung, Eun Joo; Kihan, Chung; Kim, Choong Won

doi:10.5483/bmbrep.2017.50.9.087

Cited by 11 publications

(9 citation statements)

References 29 publications

(37 reference statements)

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“…In human gastric adenocarcinoma, TXNDC5 is elevated in most of the examined samples and significantly high level of TXNDC5 is observed especially in poorly differentiated cancer 32 . In prostate tumors, TXNDC5 is upregulated in androgen naïve prostate cancer and castration-resistant prostate cancer 33, 34. Taken together, these studies suggest that TXNDC5 is highly expressed in different types of human tumors and may play a potential role in cancer development.…”

Section: Txndc5 and Cancermentioning

confidence: 71%

A critical role of the thioredoxin domain containing protein 5 (TXNDC5) in redox homeostasis and cancer development

et al. 2018

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Correct folding of nascent peptides occurs in the endoplasmic reticulum (ER). It is a complicate process primarily accomplished by the coordination of multiple redox proteins including members of the protein disulfide isomerase (PDI) family. As a critical member of the PDI family, thioredoxin domain containing protein 5 (TXNDC5) assists the folding of newly synthesized peptides to their mature form through series of disulfide bond exchange reactions. Interestingly, TXNDC5 is frequently found overexpressed in specimens of many human diseases including various types of cancer. In this review, we summarized the biochemical function of TXNDC5 in mammalian cells and the recent progress on the understanding of its role and molecular mechanisms in cancer development. Findings of TXNDC5 in the activation of intracellular signaling pathways, stimulation of cell growth & proliferation, facilitation of cell survival and modulation of extracellular matrix to affect cancer cell invasion and metastasis are reviewed. These published studies suggest that strategies of targeting TXNDC5 can be developed as potentially valuable methods for the treatment of certain types of cancer in patients.

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Section: Txndc5 and Cancermentioning

confidence: 71%

A critical role of the thioredoxin domain containing protein 5 (TXNDC5) in redox homeostasis and cancer development

et al. 2018

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“…TXN1 has been found to be upregulated in several cancers, including prostate, colon and gastric cancer, to promote cancer progression and predict poor prognosis [37][38][39]. Thioredoxin domain containing 5 (TXNDC5) is also implicated in the regulation of cancer progression of hepatocellular carcinoma, prostate cancer, and colorectal cancer [40][41][42]. TXNDC9 is involved in cancer progression as well.…”

Section: Discussionmentioning

confidence: 99%

Thioredoxin domain-containing protein 9 protects cells against UV-B-provoked apoptosis via NF-κB/p65 activation in cutaneous squamous cell carcinoma

XIAO¹,

Xu²,

WANG³

et al. 2023

Oncology Research

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Cutaneous squamous cell carcinoma (cSCC), a type of non-melanoma skin cancer (NMSC), is the most common malignancy worldwide. Thioredoxin (TXN) domain-containing protein 9 (TXNDC9) is a member of the TXN family that is important in cell differentiation. However, the biological function of this protein in cancer, particularly cSCC, is still unknown. In the present study, our experiments revealed the protective effects of TXNDC9 on UV-B-irritated cSCC cells. The initial findings showed that TXNDC9 is significantly upregulated in cSCC tissue and cells compared to normal skin tissue and keratinocytes. UV-B radiation robustly induces the expression of TXNDC9, and UV-B-induced cSCC cell death is boosted by TXNDC9 deficiency. Moreover, cSCC cells lacking TXNDC9 displayed attenuated activation of the NF-κB pathway. Additional studies by inhibiting TXNDC9 confirmed this finding, as TXNDC9 deficiency attenuated UV-B radiation-induced translocation of NF-κB p65 from the cytoplasm to the nucleus of cSCC. In conclusion, our work demonstrates the biological roles of TXNDC9 in cSCC progression and may provide a novel therapeutic target to treat cSCC in the future.

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“…In recent years, studies have shown that statin-induced cancer cell apoptosis is involved in regulating many apoptosis signaling pathways. Jung et al found that simvastatin activated caspase-8, caspase-3 and caspase-9 in prostate cancer cells and induced apoptosis 58 . Studies from Wang et al showed that simvastatin induced apoptosis of breast cancer cells via reducing the activity of PI3K/AKT 59 .…”

Section: Statins Are Potential Anticancer Agentsmentioning

confidence: 99%

Pleiotropic use of Statins as non-lipid-lowering drugs

Zhang¹,

Dong²,

2020

Int. J. Biol. Sci.

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Statins, known as HMG-CoA reductase (HMGCR) inhibitors, have primarily been utilized for metabolic and angiographic medical applications because of their cholesterol-lowering effects. Similar to other drugs, statins may also induce a series of potential side effects. Statins inhibit the HMGCR (rate-limiting enzyme) activity in early stages of mevalonate pathway and then indirectly affect a number of intermediate products, including non-sterol isoprenoids (coenzyme Q10, dolichol etc.), which can result in impaired functions of body organs. Recently, scores of studies have uncovered additional functional mechanisms of statins in other diseases, such as diabetes mellitus, nervous system diseases, coronary heart disease, inflammation and cancers. This review aims to summarize the positive and adverse mechanisms of statin therapy. Statin care should be taken in the treatment of many diseases including cancers. Since the underlying mechanisms are not fully elucidated, future studies should spend more time and efforts on basic research to explore the mechanisms of statins.

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Identification of simvastatin-regulated targets associated with JNK activation in DU145 human prostate cancer cell death signaling

Cited by 11 publications

References 29 publications

A critical role of the thioredoxin domain containing protein 5 (TXNDC5) in redox homeostasis and cancer development

A critical role of the thioredoxin domain containing protein 5 (TXNDC5) in redox homeostasis and cancer development

Thioredoxin domain-containing protein 9 protects cells against UV-B-provoked apoptosis via NF-κB/p65 activation in cutaneous squamous cell carcinoma

Pleiotropic use of Statins as non-lipid-lowering drugs

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