Abstract:
:Psoriasis is an autoimmune skin disease, where chronic immune responses due to exaggerated cytokine signaling, abnormal differentiation, and evasion of keratinocytes apoptosis plays a crucial role in mediating abnormal keratinocytes hyperproliferation. From the therapeutic perspective, the molecules with strong anti-proliferative and anti-inflammatory properties could have tremendous relevance. In this study, we demonstrated that piperlongumine (PPL) treatment effectively abrogated the hyperproliferation and differentiation of keratinocytes by inducing ROS-mediated late apoptosis with loss of mitochondrial membrane potential. Besides, the arrest of cell cycle was found at Sub-G1 phase as a result of DNA fragmentation. Molecularly, inhibition of STAT3 and Akt signaling was observed with a decrease in proliferative markers such as PCNA, ki67, and Cyclin D1 along with anti-apoptotic Bcl-2 protein expression. Keratin 17 is a critical regulator of keratinocyte differentiation, and it was found to be downregulated with PPL significantly. Furthermore, prominent anti-inflammatory effects were observed by inhibition of lipopolysaccharide (LPS)/Imiquimod (IMQ)-induced p65 NF-κB signaling cascade and strongly inhibited the production of cytokine storm involved in psoriasis-like skin inflammation, thus led to the restoration of normal epidermal architecture with reduction of epidermal hyperplasia and splenomegaly. In addition, PPL epigenetically inhibited histone-modifying enzymes, which include histone deacetylases (HDACs) of class I (HDAC1-4) and class II (HDAC6) evaluated by immunoblotting and HDAC enzyme assay kit. In addition, our results show that PPL effectively inhibits the nuclear translocation of p65 and a histone modulator HDAC3, thus sequestered in the cytoplasm of macrophages. Furthermore, PPL effectively enhanced the protein-protein interactions of HDAC3 and p65 with IκBα, which was disrupted by LPS stimulation and were evaluated by Co-IP and molecular modeling. Collectively, our findings indicate that piperlongumine may serve as an anti-proliferative and anti-inflammatory agent and could serve as a potential therapeutic option in treating psoriasis.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Thatikonda S,Pooladanda V,Sigalapalli DK,Godugu Cdoi
10.1038/s41419-019-2212-ysubject
Has Abstractpub_date
2020-01-10 00:00:00pages
21issue
1issn
2041-4889pii
10.1038/s41419-019-2212-yjournal_volume
11pub_type
杂志文章abstract::Epidermal keratinocyte differentiation on the body surface is a carefully choreographed process that leads to assembly of a barrier that is essential for life. Perturbation of keratinocyte differentiation leads to disease. Activator protein 1 (AP1) transcription factors are key controllers of this process. We have sho...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.21
更新日期:2015-02-19 00:00:00
abstract::Osteoblasts and adipocytes are differentiated from common mesenchymal stem cells (MSCs) in processes which are tightly controlled by various growth factors, signaling molecules, transcriptional factors and microRNAs. Recently, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) was identified as a ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.485
更新日期:2014-11-20 00:00:00
abstract::It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.122
更新日期:2014-04-10 00:00:00
abstract::Treatment options for necrotizing enterocolitis (NEC) remain inadequate. Here we examined if and how prolyl hydroxylase 2 (PHD2) silencing enhances the paracrine effects of bone-marrow-derived mesenchymal stem cells (BM-MSCs) on NEC. In this study, BM-MSCs were transduced with lentiviruses containing GFP (GFP-MSC) or ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2378-3
更新日期:2020-03-16 00:00:00
abstract::Only a few types of inflammasomes have been described in central nervous system cells. Among these, the absent in melanoma 2 (AIM2) inflammasome is primarily found in neurons, is highly specific and can be activated only by double-stranded DNA. Although it has been demonstrated that the AIM2 inflammasome is activated ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2248-z
更新日期:2020-01-30 00:00:00
abstract::Hepatocellular carcinoma (HCC) represents the second cause of cancer-related mortality worldwide and is associated with poor prognosis, especially in patients not amenable for curative treatments. The multi-kinase inhibitor sorafenib represents the first-line treatment option for advanced HCC; nevertheless, its effect...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0076-6
更新日期:2018-01-05 00:00:00
abstract::Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially of the lead compound Triapine. During the last years, a novel subclass of anticancer thiosemicarbazones has attracted substantial interest ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1102-z
更新日期:2018-10-15 00:00:00
abstract::A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03151-z
更新日期:2020-11-06 00:00:00
abstract::Induction of lethal autophagy has become a strategy to eliminate glioma cells, but it remains elusive whether autophagy contributes to cell death via causing mitochondria damage and nuclear translocation of apoptosis inducing factor (AIF). In this study, we find that silibinin induces AIF translocation from mitochondr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02866-3
更新日期:2020-08-14 00:00:00
abstract:: ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1120-x
更新日期:2018-10-22 00:00:00
abstract::Intrinsic apoptosis relies on the ability of the BCL-2 family to induce the formation of pores on the outer mitochondrial membrane. Previous studies have shown that both BAX and BAK are essential during murine embryogenesis, and reports in human cancer cell lines identified non-canonical roles for BAX and BAK in mitoc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03002-x
更新日期:2020-09-25 00:00:00
abstract::Skeletal muscle atrophy is one of the clinical symptoms of myotonic dystrophy type 1 (DM1). A decline in skeletal muscle regeneration is an important contributor to muscle atrophy. Skeletal muscle satellite cells (SSCs) drive skeletal muscle regeneration. Increased autophagy can reduce the proliferative capacity of SS...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02756-8
更新日期:2020-07-18 00:00:00
abstract::Apoptosis is considered a crucial part of the host defense system in oysters according to previous reports; however, the exact process by which this occurs remains unclear. Besides, mitochondrial apoptosis is the primary method of apoptosis in vertebrate cells, but has been poorly studied in invertebrates and is quite...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.307
更新日期:2017-07-06 00:00:00
abstract::MicroRNAs have emerged as important post-transcriptional regulators of gene expression and are involved in diverse diseases and cellular process. Decreased expression of miR-181a has been observed in the patients with coronary artery disease, but its function and mechanism in atherogenesis is not clear. This study was...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1599-9
更新日期:2019-05-07 00:00:00
abstract::Breast cancer is the most significant threat to female health. Breast cancer metastasis is the major cause of mortality in breast cancer patients. To fully unravel the molecular mechanisms that underlie the breast cancer cell metastasis is critical for developing strategies to improve survival and prognosis in breast ...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-020-02954-4
更新日期:2020-09-14 00:00:00
abstract::Hepatocellular carcinoma is the sixth most common cancer and gives rise to numerous deaths around the world every year. However, the molecular mechanism that controls hepatocarcinogenesis remains largely unknown. Here we found out an uncharacterized long noncoding RNA named lncAKHE. We found that lncAKHE was highly ex...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0554-5
更新日期:2018-05-01 00:00:00
abstract::Betulinic acid (BA) exhibits cytotoxic activity against some cancer cells. However, the molecular mechanism of BA against CRC cells was little reported. Here, we proved that BA elicited CRC cells' growth inhibition and apoptosis in a dose-dependent manner. In addition, BA treatment induced autophagy via inhibiting the...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.485
更新日期:2017-10-05 00:00:00
abstract::The subversion of the normal function exerted by the cellular prion protein (PrP(C)) in neurons by pathogenic prions is assumed to have a central role in the pathogenesis of transmissible spongiform encephalopathies. Using two murine models of prion infection, the 1C11 neuronal cell line and neurospheres, we document ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.195
更新日期:2013-01-10 00:00:00
abstract::Since publication of this paper, the authors have noticed that there were errors in Fig. 2A (the GAPDH of Mel-CV, Mel-CV.S, Mel-RMu and Mel-RMu.S), Fig. 2C (the GAPDH of Mel-CV.S and Mel-RMu.S), Fig. 3F (the GAPDH of Mel-CV.S and Mel-RMu.S), Fig. 3J(the GAPDH of Mel-RMu.S), Fig. 5C (the ERK1/2 of patient#3(post)), and...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-1301-2
更新日期:2019-03-05 00:00:00
abstract::Gallbladder cancer (GBC) is one of the most common malignancy of the biliary tract characterized by its high chemoresistant tendency. Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, inv...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.178
更新日期:2017-05-11 00:00:00
abstract::Colon cancer is one of the three common malignant tumors, with a lower survival rate. Ipatasertib, a novel highly selective ATP-competitive pan-Akt inhibitor, shows a strong antitumor effect in a variety of carcinoma, including colon cancer. However, there is a lack of knowledge about the precise underlying mechanism ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0943-9
更新日期:2018-09-05 00:00:00
abstract::Inhibition of tumor suppressive signaling is linked to cancer progression, metastasis and epithelial-mesenchymal transition (EMT). Transforming growth factor-β1 (TGF-β)/Smad signaling plays an important role in tumor suppression. Kruppel-like-factor 17 (KLF17) is a negative regulator of metastasis and EMT. However, un...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.48
更新日期:2015-03-12 00:00:00
abstract::Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A (RASSF1A) has been confirmed to be a key event in NPC progression; however, little is known about the effects or ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03054-z
更新日期:2020-10-14 00:00:00
abstract::The aim of the present report was to investigate whether, in the mammalian spinal cord, cell death induced by transient excitotoxic stress could trigger activation and proliferation of endogenous neuroprogenitor cells as a potential source of a lesion repair process and the underlying time course. Because it is diffic...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.431
更新日期:2013-10-31 00:00:00
abstract::Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of N...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.132
更新日期:2017-03-23 00:00:00
abstract::Following publication of this article, it was brought to our attention that there was a typo in the References (reference number 43) whereby the first author's name was misspelled. The correct citation is provided below. We apologize for the inconvenience. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-2029-8
更新日期:2019-10-22 00:00:00
abstract::PTPL1 is a non-receptor protein tyrosine phosphatase involved in apoptosis regulation, although controversial findings have been reported in different cancer types. We report here a proapoptotic role for PTPL1 in PC3 and LNCaP prostate cancer cells, as its absence induces apoptosis resistance upon treatment with diffe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.90
更新日期:2013-04-04 00:00:00
abstract::Reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress are paradoxically implicated in myocardial ischemia/reperfusion (I/R) injury and cardioprotection. However, the precise interpretation for the dual roles of ROS and its relationship with the ER stress during I/R remain elusive. Here we investigated th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.267
更新日期:2014-06-19 00:00:00
abstract::Melanoma is a kind of tumor that originates from melanocytes and is characterized by chemoresistance and distant metastasis. Although the complete pathogenesis of melanoma remains unclear, increasing evidence suggests that circular RNAs (circRNAs) may be involved. In the present study, we identified a circular RNA, ci...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2444-x
更新日期:2020-04-23 00:00:00
abstract::Reactive gliosis is an early pathological feature common to most neurodegenerative diseases, yet its regulation and impact remain poorly understood. Normally astrocytes maintain a critical homeostatic balance. After stress or injury they undergo rapid parainflammatory activation, characterized by hypertrophy, and incr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.277
更新日期:2016-09-29 00:00:00