scholarly journals Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1418
Author(s):  
Richard B. Parsons ◽  
Paul D. Facey
Keyword(s):  
Cancer Survival ◽  
Cell Function ◽  
Cancer Therapeutics ◽  
Metabolic Enzyme ◽  
Post Translational Modification ◽  
Anti Cancer ◽  
Cancer Phenotype ◽  
Non Coding Rnas ◽  
First Time ◽  
Insight Into

Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for NNMT in cancer survival, metastasis, and drug resistance. In this review, we discuss the evidence supporting a role for NNMT in the progression of the cancer phenotype and how it achieves this by driving the activity of pro-oncogenic NAD+-consuming enzymes. We also describe how increased NNMT activity supports the Warburg effect and how it promotes oncogenic changes in gene expression. We discuss the regulation of NNMT activity in cancer cells by both post-translational modification of the enzyme and transcription factor binding to the NNMT gene, and describe for the first time three long non-coding RNAs which may play a role in the regulation of NNMT transcription. We complete the review by discussing the development of novel anti-cancer therapeutics which target NNMT and provide insight into how NNMT-based therapies may be best employed clinically.

The application and mechanism of PD pathway blockade for cancer therapy

2017 ◽  
Vol 94 (1107) ◽  
pp. 53-60 ◽  
Author(s):  
Xing Wang ◽  
Shan Huang ◽  
Ya Zhang ◽  
Lin Zhu ◽  
Xiaoliang Wu
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Cancer Therapeutics ◽  
Toxicity Profile ◽  
Inhibitory Pathway ◽  
Tumour Immunity ◽  
Cancer Types ◽  
Antigen Presenting ◽  
Major Progress ◽  
Insight Into

Research in cancer therapeutics has achieved major progress in the understanding of the tumour-immunity cycle, which controls the delicate balance between the immune system and tumour. Identification of cancer cell T-cell inhibitory signals, including PD-L1, has generated novel insight into how to reinvigorate the patients’ immune cells to respond to a variety of tumour types. PD-1 and PD-L1 (PD) inhibitory pathway blockade appears to a highly promising therapy and could accomplish durable anti-tumour responses with a reasonable toxicity profile. Some of the FDA-approved mAbs can reverse the negative regulators from tumour cells and antigen presenting cells of T-cell function to treat some cancer types by blocking the PD signalling pathway,especially advanced solid tumours. Emerging clinical data suggest that cancer immunotherapy will become a significant part of the clinical treatment of cancer.

scholarly journals Physical connectivity mapping by circular permutation of human telomerase RNA reveals new regions critical for activity and processivity

2015 ◽  
pp. MCB.00794-15 ◽  
Author(s):  
Melissa A. Mefford ◽  
David C. Zappulla
Keyword(s):  
Cancer Therapeutics ◽  
Telomerase Activity ◽  
Circular Permutation ◽  
Telomerase Rna ◽  
Recognition Element ◽  
Circular Permutations ◽  
Anti Cancer ◽  
Human Telomerase ◽  
First Time

Telomerase is a specialized ribonucleoprotein complex that extends the 3’ ends of chromosomes to counteract telomere shortening. However, increased telomerase activity is associated with ∼90% of human cancers. The telomerase enzyme minimally requires an RNA (hTR) and a specialized reverse transcriptase protein (TERT) for activityin vitro. Understanding the structure-function relationships within hTR has important implications for human disease. For the first time, we have tested the physical-connectivity requirements in the 451-nucleotide hTR RNA using circular permutations, which reposition the 5’ and 3’ ends. Our extensivein vitroanalysis identified three classes of hTR circular permutants with altered function. First, circularly permuting 3’ of the template causes specific defects in repeat-addition processivity, revealing that the template-recognition element found in ciliates is conserved in human telomerase RNA. Second, seven circular permutations residing within the catalytically important core and CR4/5 domains completely abolish telomerase activity, unveiling mechanistically critical portions of these domains. Third, several circular permutations between the core and CR4/5 significantly increase telomerase activity. Our extensive circular permutation results provide insights into the architecture and coordination of human hTR and highlight where the RNA could be targeted for the development of anti-aging and anti-cancer therapeutics.

Novel Mechanistic Insights into the Anti-cancer Mode of Arsenic Trioxide

2020 ◽  
Vol 20 (2) ◽  
pp. 115-129 ◽  
Author(s):  
Md Wahiduzzaman ◽  
Akinobu Ota ◽  
Yoshitaka Hosokawa
Keyword(s):  
Arsenic Trioxide ◽  
Molecular Mechanisms ◽  
Cancer Therapeutics ◽  
Cancer Drug ◽  
Clinical Settings ◽  
Cancer Therapies ◽  
Cellular Models ◽  
Anti Cancer ◽  
Cancer Phenotype

Arsenic, a naturally-occurring toxic element, and a traditionally-used drug, has received a great deal of attention worldwide due to its curative anti-cancer properties in patients with acute promyelocytic leukemia. Among the arsenicals, arsenic trioxide has been most widely used as an anti-cancer drug. Recent advances in cancer therapeutics have led to a paradigm shift away from traditional cytotoxic drugs towards the targeting of proteins closely associated with driving the cancer phenotype. Due to the diverse anti-cancer effects of ATO on different types of malignancies, numerous studies have made efforts to uncover the mechanisms of ATO-induced tumor suppression. From in vitro cellular models to studies in clinical settings, ATO has been extensively studied. The outcomes of these studies have opened doors to establishing improved molecular-targeted therapies for cancer treatment. The efficacy of ATO has been augmented by combination with other drugs. In this review, we discuss recent arsenic-based cancer therapies and summarize the novel underlying molecular mechanisms of the anti-cancer effects of ATO.

scholarly journals Regulation of a PRMT5/NF-κB Axis by Phosphorylation of PRMT5 at Serine 15 in Colorectal Cancer

2020 ◽  
Vol 21 (10) ◽  
pp. 3684 ◽  
Author(s):  
Antja-Voy Hartley ◽  
Benlian Wang ◽  
Guanglong Jiang ◽  
Han Wei ◽  
Mengyao Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Target Genes ◽  
Cancer Therapeutics ◽  
Hek293 Cells ◽  
Anti Cancer ◽  
Signaling Axis ◽  
Phosphorylation Event ◽  
Promoter Occupancy ◽  
Highly Correlated ◽  
First Time

The overexpression of PRMT5 is highly correlated to poor clinical outcomes for colorectal cancer (CRC) patients. Importantly, our previous work demonstrated that PRMT5 overexpression could substantially augment activation of the nuclear factor kappa B (NF-κB) via methylation of arginine 30 (R30) on its p65 subunit, while knockdown of PRMT5 showed the opposite effect. However, the precise mechanisms governing this PRMT5/NF-κB axis are still largely unknown. Here, we report a novel finding that PRMT5 is phosphorylated on serine 15 (S15) in response to interleukin-1β (IL-1β) stimulation. Interestingly, we identified for the first time that the oncogenic kinase, PKCι could catalyze this phosphorylation event. Overexpression of the serine-to-alanine mutant of PRMT5 (S15A), in either HEK293 cells or CRC cells HT29, DLD1, and HCT116 attenuated NF-κB transactivation compared to WT-PRMT5, confirming that S15 phosphorylation is critical for the activation of NF-κB by PRMT5. Furthermore, the S15A mutant when compared to WT-PRMT5, could downregulate a subset of IL-1β-inducible NF-κB-target genes which correlated with attenuated promoter occupancy of p65 at its target genes. Additionally, the S15A mutant reduced IL-1β-induced methyltransferase activity of PRMT5 and disrupted the interaction of PRMT5 with p65. Furthermore, our data indicate that blockade of PKCι-regulated PRMT5-mediated activation of NF-κB was likely through phosphorylation of PRMT5 at S15. Finally, inhibition of PKCι or overexpression of the S15A mutant attenuated the growth, migratory, and colony-forming abilities of CRC cells compared to the WT-PRMT5. Collectively, we have identified a novel PKCι/PRMT5/NF-κB signaling axis, suggesting that pharmacological disruption of this pivotal axis could serve as the basis for new anti-cancer therapeutics.

Aleksey Peshkov as an editor of Samarskaya Gazeta

2020 ◽  
pp. 128-138
Author(s):  
A. S. Bik-Bulatov
Keyword(s):  
Local History ◽  
Organizational Skills ◽  
First Time ◽  
New Evidence ◽  
Insight Into ◽  
Shed Light

The article uses little known letters of M. Gorky, many of which were published for the first time in 1997, as well as findings of Samara-based experts in local history to shed light on the writer’s work as editor-in-chief of the Samarskaya Gazeta newspaper in 1895. The researcher introduces hitherto unstudied reminiscences of the journalist D. Linyov (Dalin) about this period, which reference a letter by Gorky, now lost. The paper details a newly discovered episode of Gorky’s professional biography as a journalist: it concerns his campaign against a Samara ‘she-wolf,’ the madam of a local brothel A. Neucheva. Linyov’s reminiscences turn out to be an important and interesting source, offering an insight into the daily grind of the young editor Gorky, providing new evidence of his excellent organizational skills, and describing his moral and social stance. The author presents his work in the context of a recently initiated broader discussion about the need to map out all Russian periodicals for the period until 1917, as well as all research devoted to individual publications.

Resveratrol: A new potential therapeutic agent for melanoma?

2019 ◽  
Vol 26 ◽  
Author(s):  
Mohamad Hossein Pourhanifeh ◽  
Kazem Abbaszadeh-Goudarzi ◽  
Mohammad Goodarzi ◽  
Sara G.M. Piccirillo ◽  
Alimohammad Shafiee ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Therapeutic Agent ◽  
Current Knowledge ◽  
Treatment Resistance ◽  
Anti Cancer ◽  
Apoptosis Inducer ◽  
Life Threatening ◽  
First Time

: Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard anti-melanomatreatments such as chemotherapy, and 5-year survival rate of cases with melanoma who have metastatic form of disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approachesthat couldenhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. : Herein, for first time, we summarize current knowledge of anti-cancerous activities of resveratrol in melanoma.

Animal Venoms have Potential to Treat Cancer

2019 ◽  
Vol 18 (30) ◽  
pp. 2555-2566 ◽  
Author(s):  
Bhaswati Chatterjee
Keyword(s):  
Cancer Therapeutics ◽  
Sea Anemones ◽  
Anticancer Activities ◽  
Inhibition Of Proliferation ◽  
Cycle Arrest ◽  
Venomous Animals ◽  
Anti Cancer ◽  
Cancerous Cells ◽  
Animal Venoms ◽  
Proteins And Peptides

The resistance to chemotherapeutics by the cancerous cells has made its treatment more complicated. Animal venoms have emerged as an alternative strategy for anti-cancer therapeutics. Animal venoms are cocktails of complex bioactive chemicals mainly disulfide-rich proteins and peptides with diverse pharmacological actions. The components of venoms are specific, stable, and potent and have the ability to modify their molecular targets thus making them good therapeutics candidates. The isolation of cancer-specific components from animal venoms is one of the exciting strategies in anti-cancer research. This review highlights the identified venom peptides and proteins from different venomous animals like snakes, scorpions, spiders, bees, wasps, snails, toads, frogs and sea anemones and their anticancer activities including inhibition of proliferation of cancer cells, their invasion, cell cycle arrest, induction of apoptosis and the identification of involved signaling pathways.

The Applications of Targeting Anti-Cancer Agents in Cancer Therapeutics

2015 ◽  
Vol 15 (7) ◽  
pp. 869-880 ◽  
Author(s):  
Guang-Chun Sun ◽  
X Yang ◽  
Yan Yu ◽  
Dai-Wei Zhao
Keyword(s):  
Cancer Therapeutics ◽  
Anti Cancer

scholarly journals Comparative Study of Chemical Compositions and Antioxidant Capacities of Oils Obtained from 15 Macadamia (Macadamia integrifolia) Cultivars in China

Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1031
Author(s):  
Xixiang Shuai ◽  
Taotao Dai ◽  
Mingshun Chen ◽  
Ruihong Liang ◽  
Liqing Du ◽  
...  
Keyword(s):  
Palmitoleic Acid ◽  
Linear Regression Analysis ◽  
Monounsaturated Fatty Acids ◽  
Multiple Linear Regression Analysis ◽  
Chemical Compositions ◽  
Macadamia Integrifolia ◽  
Antioxidant Capacities ◽  
Squalene Content ◽  
First Time ◽  
Insight Into

The planting area of macadamia in China accounted for more than one third of the world’s planted area. The lipid compositions, minor components, and antioxidant capacities of fifteen varieties of macadamia oil (MO) in China were comparatively investigated. All varieties of MO were rich in monounsaturated fatty acids, mainly including oleic acid (61.74–66.47%) and palmitoleic acid (13.22–17.63%). The main triacylglycerols of MO were first time reported, including 19.2–26.1% of triolein, 16.4–18.2% of 1-palmitoyl-2,3-dioleoyl-glycerol, and 11.9–13.7% of 1-palmitoleoyl-2-oleoyl-3-stearoyl-glycerol, etc. The polyphenol, α-tocotrienol and squalene content varied among the cultivars, while Fuji (791) contained the highest polyphenols and squalene content. Multiple linear regression analysis indicated the polyphenols and squalene content positively correlated with the antioxidant capacity. This study can provide a crucial directive for the breeding of macadamia and offer an insight into industrial application of MO in China.

scholarly journals Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3530
Author(s):  
Penn Muluhngwi ◽  
Carolyn M. Klinge
Keyword(s):  
Breast Cancer ◽  
Cancer Survival ◽  
Expression Patterns ◽  
Endocrine Resistance ◽  
Estrogen Receptor Α ◽  
Resistant Cell ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Non Coding Rnas ◽  
Mcf 7

Despite improvements in the treatment of endocrine-resistant metastatic disease using combination therapies in patients with estrogen receptor α (ERα) primary tumors, the mechanisms underlying endocrine resistance remain to be elucidated. Non-coding RNAs (ncRNAs), including microRNAs (miRNA) and long non-coding RNAs (lncRNA), are targets and regulators of cell signaling pathways and their exosomal transport may contribute to metastasis. Previous studies have shown that a low expression of miR-29a-3p and miR-29b-3p is associated with lower overall breast cancer survival before 150 mos. Transient, modest overexpression of miR-29b1-3p or miR-29a-3p inhibited MCF-7 tamoxifen-sensitive and LCC9 tamoxifen-resistant cell proliferation. Here, we identify miR-29b-1/a-regulated and non-regulated differentially expressed lncRNAs in MCF-7 and LCC9 cells using next-generation RNA seq. More lncRNAs were miR-29b-1/a-regulated in LCC9 cells than in MCF-7 cells, including DANCR, GAS5, DSCAM-AS1, SNHG5, and CRND. We examined the roles of miR-29-regulated and differentially expressed lncRNAs in endocrine-resistant breast cancer, including putative and proven targets and expression patterns in survival analysis using the KM Plotter and TCGA databases. This study provides new insights into lncRNAs in endocrine-resistant breast cancer.

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