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Dong-Gyu Leem, Ji-Sun Shin, Kyung-Tack Kim, Sang Yoon Choi, Myung-Hee Lee, Kyung-Tae Lee
A previous study reported that a novel dammarane-type triterpene saponin, ginsenoside-Rg18, derived from the root of Panax ginseng , displayed hydroxyl radical scavenging, anti-bacterial and cytotoxic activities. However, the underlying molecular mechanisms of its anti-proliferative effect on non-small cell lung cancer (NSCLC) A549 cells remains unclear. In the present study, it was determined that Rg18 inhibited the proliferation of A549 cells with a half-maximal inhibitory concentration of 150 µM. Flow cytometry analysis indicated that cell cycle progression was blocked by Rg18 at G1 phase in A549 cells, which was accompanied by downregulation of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin D1, cyclin D2, cyclin E and phosphorylated retinoblastoma protein expression at the protein level...
April 2018: Oncology Letters
Amit Kumar, Mohanraj Gopalswamy, Annika Wolf, David J Brockwell, Mechthild Hatzfeld, Jochen Balbach
Cell cycle progression is tightly regulated by cyclin-dependent kinases (CDKs). The ankyrin-repeat protein p19INK4d functions as a key regulator of G1/S transition; however, its molecular mode of action is unknown. Here, we combine cell and structural biology methods to unravel the mechanism by which p19INK4d controls cell cycle progression. We delineate how the stepwise phosphorylation of p19INK4d Ser66 and Ser76 by cell cycle-independent (p38) and -dependent protein kinases (CDK1), respectively, leads to local unfolding of the three N-terminal ankyrin repeats of p19INK4d This dissociates the CDK6-p19INK4d inhibitory complex and, thereby, activates CDK6...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Wenjie Deng, Yueyuan Wang, Shuo Zhao, Yujie Zhang, Yan Chen, Xuyang Zhao, Lei Liu, Shixiu Sun, Lin Zhang, Bixing Ye, Jun Du
Molecule interacting with CasL 1 (MICAL1) is a multidomain flavoprotein mono-oxygenase that strongly involves in cytoskeleton dynamics and cell oxidoreduction metabolism. Recently, results from our laboratory have shown that MICAL1 modulates reactive oxygen species (ROS) production, and the latter then activates phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (Akt) signalling pathway which regulates breast cancer cell invasion. Herein, we performed this study to assess the involvement of MICAL1 in breast cancer cell proliferation and to explore the potential molecular mechanism...
March 10, 2018: Journal of Cellular and Molecular Medicine
Xiaoli Hou, Yongzhao Zhang, Wei Li, Alexander J Hu, Chi Luo, Wenhui Zhou, Jamie K Hu, Stefano G Daniele, Jinfeng Wang, Jinghao Sheng, Yongsheng Fan, Andrew S Greenberg, Stephen R Farmer, Miaofen G Hu
Whereas white adipose tissue depots contribute to the development of metabolic diseases, brown and beige adipose tissue has beneficial metabolic effects. Here we show that CDK6 regulates beige adipocyte formation. We demonstrate that mice lacking the CDK6 protein or its kinase domain (K43M) exhibit significant increases beige cell formation, enhanced energy expenditure, better glucose tolerance, and improved insulin sensitivity, and are more resistant to high-fat diet-induced obesity. Re-expression of CDK6 in Cdk6-/- mature or precursor cells, or ablation of RUNX1 in K43M mature or precursor cells, reverses these phenotypes...
March 9, 2018: Nature Communications
Ping Hu, Zhicai Zuo, Fengyuan Wang, Xi Peng, Ke Guan, Hang Li, Jing Fang, Hengmin Cui, Gang Su, Ping Ouyang, Yi Zhou
Aflatoxin B1 (AFB1 ) is a naturally occurring secondary metabolites of Aspergillus flavus and Aspergillus parasiticus, and is the most toxic form of aflatoxins. Selenium (Se) with antioxidant and detoxification functions is one of the essential trace elements for human beings and animals. This study aims to evaluate the protective effects of Se on AFB1 -induced tissue damage and cell cycle arrest in bursa of Fabricius (BF) of chickens. The results showed that a dietary supplement of 0.4 mg·kg-1 Se alleviated the histological lesions induced by AFB1 , as demonstrated by decreasing vacuoles and nuclear debris, and relieving oxidative stress...
March 6, 2018: Biological Trace Element Research
Dominika Czaplinska, Monika Górska, Kamil Mieczkowski, Grazyna Peszynska-Sularz, Anna J Zaczek, Hanna M Romanska, Rafal Sadej
INTRODUCTION: Triple-negative breast cancer (TNBC), representing over 15% of all breast cancers, has a poorer prognosis than other subtypes. There is no effective targeted treatment available for the TNBC sufferers. Ribosomal S6 kinases (RSKs) have been previously proposed as drug targets for TNBC based on observations that 85% of these tumors express activated RSKs. MATERIALS AND METHODS: Herein we examined an involvement of RSK1 (p90 ribosomal S6 kinase 1) in a regulation of TNBC growth and metastatic spread in an animal model, which closely imitates human disease...
March 2, 2018: Folia Histochemica et Cytobiologica
Sadakatsu Ikeda, Igor F Tsigelny, Åge A Skjevik, Yuko Kono, Michel Mendler, Alexander Kuo, Jason K Sicklick, Gregory Heestand, Kimberly C Banks, AmirAli Talasaz, Richard B Lanman, Scott Lippman, Razelle Kurzrock
BACKGROUND: Because imaging has a high sensitivity to diagnose hepatocellular carcinoma (HCC) and tissue biopsies carry risks such as bleeding, the latter are often not performed in HCC. Blood-derived circulating tumor DNA (ctDNA) analysis can identify somatic alterations, but its utility has not been characterized in HCC. MATERIALS AND METHODS: We evaluated 14 patients with advanced HCC (digital ctDNA sequencing [68 genes]). Mutant relative to wild-type allele fraction was calculated...
February 27, 2018: Oncologist
Shariq S Ansari, Ashwini K Sharma, Michael Zepp, Elizabet Ivanova, Frank Bergmann, Rainer König, Martin R Berger
The TCGA database was analyzed to identify deregulation of cell cycle genes across 24 cancer types and ensuing effects on patient survival. Pan-cancer analysis showed that head and neck squamous cell carcinoma (HNSCC) ranks amongst the top four cancers showing deregulated cell cycle genes. Also, the median gene expression of all CDKs and cyclins in HNSCC patient samples was higher than that of the global gene expression. This was verified by IHC staining of CCND1 from HNSCC patients. When evaluating the quartiles with highest and lowest expression, increased CCND1/CDK6 levels had negative implication on patient survival...
January 19, 2018: Oncotarget
Qiao-Li Lv, Hui-Ting Zhu, Xiao-Hua Cheng, Hong-Mi Li, Hong-Hao Zhou, Shu-Hui Chen
Emerging studies show that dysregulated miRNAs are implicated in tumorigenesis and progression of various cancers. MiRNA-320c, an important member of miRNA-320 family, was characterized as a new candidate miRNA that suppressed the development of colorectal cancer and bladder cancer. However, the function of miRNA-320c in human glioma remained unclear. Here, we found that miRNA-320c was significantly down-regulated in glioma tissues and cell lines in contrast with normal brain tissues, being tightly related to clinical stage of glioma by qRT-PCR...
February 10, 2018: Brain Research Bulletin
Daguang Wang, Yabin Sun, Wei Li, Fei Ye, Yang Zhang, Yuchen Guo, David Y Zhang, Jian Suo
PD0332991 (palbociclib/Ibrance®) is a cyclin-dependent kinase (CDK)4/6 inhibitor that has recently been approved for the treatment of estrogen receptor‑positive advanced breast cancer. The present study investigated the antiproliferative effects of PD0332991 on gastric cancer (GC) cells and the underlying molecular mechanisms. The activity of PD0332991 was tested in several GC cell lines, including AGS, KATO‑Ⅲ, NCI‑N87 and HS746T. Growth inhibitory activity of PD0332991, alone or in combination with fluorouracil (5‑FU), was measured by MTT assay...
February 6, 2018: International Journal of Molecular Medicine
Apollinaire Ngankeu, Parvathi Ranganathan, Violaine Havelange, Deedra Nicolet, Stefano Volinia, Bayard L Powell, Jonathan E Kolitz, Geoffrey L Uy, Richard M Stone, Steven M Kornblau, Michael Andreeff, Carlo M Croce, Clara D Bloomfield, Ramiro Garzon
We previously reported that microRNA (miR)-29b is down-regulated and has a tumor suppressor role in acute myeloid leukemia (AML). However, little is known about the mechanisms responsible for miR-29b expression downregulation in AML. In this work we screened for mutations that could affect miR-29b expression. Using Sanger sequencing, we identified a germline thymidine (T) base deletion within the miR-29b-1/miR-29a cluster precursor in 16% of AML patients. Remarkably we found a significant enrichment for the presence of the miR-29 polymorphism in core binding factor (CBF) newly diagnosed AML patients (n = 61/303; 20%) with respect to age, sex and race matched controls (n = 43/402:11%, P < 0...
January 12, 2018: Oncotarget
Shalini Nath, Chhabinath Mandal, Uttara Chatterjee, Chitra Mandal
Modulation of sialylation by sialyltransferases and sialidases plays essential role in carcinogenesis. There are few reports on sialyltransferase, however, the contribution of cytosolic sialidase (Neu2) remains unexplored in pancreatic ductal adenocarcinoma (PDAC). We observed lower expression of Neu2 in different PDAC cells, patient tissues, and a significant strong association with clinicopathological characteristics. Neu2 overexpression guided drug-resistant MIAPaCa2 and AsPC1 cells toward apoptosis as evidenced by decreased Bcl2/Bax ratio, activation of caspase-3/caspase-6/caspase-8, PARP reduction, reduced CDK2/CDK4/CDK6, and cyclin-B1/cyclin-E with unaffected caspase-9...
February 12, 2018: Cell Death & Disease
Daming Sun, Hongwei Li, Shengyong Mao, Weiyun Zhu, Junhua Liu
The objective of this study was to investigate the effects of different source of starch in starter feed on small intestinal growth and endogenous glucagon-like peptide 2 (GLP-2) secretion in pre-weaned lambs. Twenty-four 10-day-old lambs were divided into three groups that were treated with different iso-starch diets containing purified cassava starch (CS, n = 8), maize starch (MS, n = 8) and pea starch (PS, n = 8). At 56 days old, there was no significant difference in final body weight (BW) of lambs among the three groups...
February 8, 2018: Journal of Animal Science
Sumi Shrestha, Anabel Sorolla, Jane Fromont, Pilar Blancafort, Gavin R Flematti
Triple negative breast cancer (TNBC) is currently the only group of breast cancers without an effective targeted therapy. Marine sponges have historically been a source of compounds with anticancer activity. In this study, we screened extracts from twenty marine sponges collected off the coast of Western Australia for cytotoxic activity against TNBC cells. One very active extract derived from the sponge Monanchora viridis was selected for bioactivity-guided fractionation. Through multiple steps of purification, we isolated a potent cytotoxic compound, which was identified as crambescidin 800 (C800)...
February 8, 2018: Marine Drugs
Roberta Bortolozzi, Elena Mattiuzzo, Luca Trentin, Benedetta Accordi, Giuseppe Basso, Giampietro Viola
Dysregulation of the cyclin D1-CDK4/CDK6 complex is frequently observed in almost all human cancer and contributes to aberrant cell proliferation and consequent tumorigenesis. Although many reports described the importance of CDK4/CDK6 in different set of human tumors, only few studies have been performed on leukemia. By gene expression analysis performed in a cohort of childhood patients affected by B-acute lymphoblastic leukemia (B-ALL) we found that both CDK4 and CDK6 are highly expressed. Moreover, Reverse Phase Protein Array (RPPA) analysis showed that cyclin D1 levels are higher in patients undergoing relapse...
February 3, 2018: Biochemical Pharmacology
Roberto R Capela de Matos, Moneeb A K Othman, Gerson M Ferreira, Elaine S Costa, Joana B Melo, Isabel M Carreira, Mariana T de Souza, Bruno A Lopes, Mariana Emerenciano, Marcelo G P Land, Thomas Liehr, Raul C Ribeiro, Maria Luiza M Silva
Myeloid neoplasms are a heterogeneous group of hematologic disorders with divergent patterns of cell differentiation and proliferation, as well as divergent clinical courses. Rare recurrent genetic abnormalities related to this group of cancers are associated with poor outcomes. One such abnormality is the MECOM gene rearrangement that typically occurs in cases with chromosome 7 abnormalities. MECOM encodes a transcription factor that plays an essential role in cell proliferation and maintenance and also in epigenetic regulation...
February 2018: Cancer Genetics
Imran Khan, Ashutosh Bahuguna, Monika Bhardwaj, Tejinder Pal Khaket, Sun Chul Kang
Carvacrol is a monoterpenoid flavonoid found abundantly in thyme plants. Its physiochemical instability and partial solubility in water is the principal limitation for its industrial use. Hence, we made a carvacrol nanoemulsion (CANE) using ultrasonication method and characterized it by dynamic light scattering (DLS) technique which revealed a negative surface charge (-29.89 mV) with 99.1 nm average droplet size. CANE effectively induced apoptosis in doxorubicin-resistant A549 lung carcinoma cells (A549 DR ) evident by the elevated expression of apoptotic proteins such as Bax, Cytochrome C, and Cleaved caspase 3 and 9...
February 6, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Da-Peng Yun, Yu-Qi Wang, De-Long Meng, Yuan-Yuan Ji, Ju-Xiang Chen, Hong-Yan Chen, Da-Ru Lu
Glioma is the most aggressive and malignant primary brain tumor in adults. In the present study, we identified a vital oncoprotein, capping actin protein, gelsolin-like (CapG), and investigated its roles in the prognosis, proliferation and metastasis in glioma. The mRNA and protein levels of CapG were significantly increased in human glioma, and higher CapG expression was an independent prognostic factor for predicting unfavorable prognosis. The expression level of CapG was found to be associated with several common molecular features of glioblastoma (GBM; WHO grade IV glioma) in The Cancer Genome Atlas (TCGA) cohort...
January 22, 2018: Oncology Reports
Minghui Liu, Hongyu Liu, Jun Chen
An uncontrolled cell cycle is an obvious marker of tumor cells. The G1‑S phase is an important restriction point in the normal cell cycle, but in cancer cells the restriction function is reduced, leading to uncontrolled cell proliferation. Two cyclin‑dependent kinases (CDKs), CDK4 and CDK6, play a crucial role in the G1‑S phase transition. Inhibitors of CDK4/6 are presently the subjects of numerous studies, and PD 0332991, an inhibitor of CDK4/6, has been used to treat hormone receptor (HR)‑positive, advanced‑stage breast cancer...
January 19, 2018: Oncology Reports
Ping Hu, Zhicai Zuo, Hang Li, Fengyuan Wang, Xi Peng, Jing Fang, Hengmin Cui, Caixia Gao, Hetao Song, Yi Zhou, Zhengli Chen
Aflatoxin B1 shows potent hepatotoxic, carcinogenic, genotoxic, immunotoxic potential in humans and many species of animals. The aim of this study was to clarify the underlying mechanism of G0G1 phase and G2M phase arrest of cell cycle in the bursa of Fabricius in broilers exposed to dietary AFB1. 144 one-day-old healthy Cobb broilers were randomly divided into two groups and fed on control diet and 0.6 mg·Kg-1 AFB1 diet for 3 weeks. Histological observation showed that AFB1 induced the increase of nuclear debris and vacuoles in lymphoid follicle of BF...
January 29, 2018: Scientific Reports
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