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apoptosis AND autophagy

Claudio Luparello, Dalia Maria Lucia Asaro, Ilenia Cruciata, Storm Hassell-Hart, Supojjanee Sansook, John Spencer, Fabio Caradonna
We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide ( N ¹-(2-aminophenyl)- N ⁸-ferrocenyloctanediamide) and its two derivatives N ¹-(2-aminophenyl)- N ⁶-ferrocenyladipamide and N ¹-(2-aminophenyl)- N ⁸-ferroceniumoctanediamide tetrafluoroborate on triple-negative MDA-MB-231 breast cancer cells. Viability/growth assays indicated that only the first two compounds at 70 μM concentration caused an approximate halving of cell number after 24 h of exposure, whereas the tetrafluoroborate derivative exerted no effect on cell survival nor proliferation...
February 13, 2019: International Journal of Molecular Sciences
Lorenza Sisinni, Michele Pietrafesa, Silvia Lepore, Francesca Maddalena, Valentina Condelli, Franca Esposito, Matteo Landriscina
The unfolded protein response (UPR) is a stress response activated by the accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER) and its uncontrolled activation is mechanistically responsible for several human pathologies, including metabolic, neurodegenerative, and inflammatory diseases, and cancer. Indeed, ER stress and the downstream UPR activation lead to changes in the levels and activities of key regulators of cell survival and autophagy and this is physiologically finalized to restore metabolic homeostasis with the integration of pro-death or/and pro-survival signals...
February 16, 2019: International Journal of Molecular Sciences
Zhipeng Xu, Zheng Li, Weizhi Wang, Yiwen Xia, Zhongyuan He, BoWen Li, Sen Wang, Xiaoxu Huang, Guangli Sun, Jianghao Xu, Lu Wang, Qiang Zhang, Qiang Li, Jialun Lv, Linjun Wang, Lu Zhang, Diancai Zhang, Hao Xu, Zekuan Xu
Increasing evidence indicates that microRNAs (miRNAs) play an important role in various tumors by regulating downstream target genes and diverse signaling pathways. Herein, we confirmed miR-1265 expression in gastric cancer (GC) using the Cancer Genome Atlas (TCGA) database and assessed the level of miR-1265 expression in clinical specimens and cell lines. We found that miR-1265 expression was negatively correlated with tumor size. Further functional analysis revealed that miR-1265 suppresses cellular proliferation and autophagy while inducing apoptosis in GC cells...
February 16, 2019: Cancer Letters
Y Dong, Y Wu, G-L Zhao, Z-Y Ye, C-G Xing, X-D Yang
OBJECTIVE: Cell autophagy reduces the sensitivity of cancer cells to therapeutic reagents in various types of human cancer. Therefore, the aim of our study was to use human colorectal cancer HCT116 cells to explore whether inhibition of autophagy by 3-Methyladenine (3-MA, an autophagy inhibitor) is able to enhance hypoxia-induced apoptosis in vitro. MATERIALS AND METHODS: HCT116 cells were treated with 3-MA, hypoxia, or 3-MA plus hypoxia, and the autophagy, apoptosis and proliferation of the HCT116 cells were investigated...
February 2019: European Review for Medical and Pharmacological Sciences
Sonia Brun, Firas Bassissi, Cindy Serdjebi, Marie Novello, Jennifer Tracz, François Autelitano, Marie Guillemot, Philippe Fabre, Jérôme Courcambeck, Christelle Ansaldi, Eric Raymond, Philipe Halfon
Among the acquired modifications in cancer cells, changes in lysosomal phenotype and functions are well described, making lysosomes a potential target for novel therapies. Some weak base lipophilic drugs have a particular affinity towards lysosomes, taking benefits from lysosomal trapping to exert anticancer activity. Here, we have developed a new lysosomotropic small molecule, GNS561, and assessed its activity in multiple in vitro intrahepatic cholangiocarcinoma models (HuCCT1 and RBE cell lines and patient-derived cells) and in a chicken chorioallantoic membrane xenograft model...
February 19, 2019: Investigational New Drugs
J Rzemieniec, A Wnuk, W Lasoń, W Bilecki, M Kajta
There are no studies examining the effects of 3,3'-diindolylmethane (DIM) in neuronal cells subjected to ischemia. Little is also known about the roles of apoptosis and autophagy as well as AhR and ERα signaling and HDACs in DIM action. We demonstrated for the first time the strong neuroprotective capacity of DIM in mouse primary hippocampal cell cultures exposed to ischemia at early and later stages of neuronal development. The protective effects of DIM were mediated via inhibition of ischemia-induced apoptosis and autophagy that was accompanied by a decrease in AhR/CYP1A1 signaling and an increase in HDAC activity...
February 18, 2019: Apoptosis: An International Journal on Programmed Cell Death
Haobin Zhao, Xixi Zhao, Shuzhen Lei, Yawen Zhang, Dongyan Shao, Chunmei Jiang, Hui Sun, Junling Shi
Two-dimensional (2D) cell culture is widely used to evaluate the potential of food compounds in anticancer activity in vitro. However, 3D culture is rarely used. In this study, we compared the obtained anticancer activity and mechanisms of iturin A, a multiple functional compound produced by Bacillus subtilis, in 2D and 3D cultures of HepG2 cells. 3D culture resulted in a much higher 50% inhibitory concentration (55.26 μM) compared to 2D culture (11.91 μM). Reactive oxygen species accumulation, autophagy, apoptosis characterized by cytochrome c release, high apoptotic protein expression and caspase activation were detected in both 2D and 3D cultures...
February 19, 2019: Food & Function
Di Wu, Wen-Yi Zhou, Xiao-Tong Lin, Lei Fang, Chuan-Ming Xie
OBJECTIVE: Bufalin has been reported to kill various types of cancer including human colorectal cancer. Our previous study demonstrated that bufalin induced cell death via autophagy in HT-29 and Caco-2 colon cancer cells, but the action of bufalin remains unclear. This study was conducted to investigate the role of bufalin in other colon cancer HCT-116 and SW620 cells as well as its potential mechanism. METHODS: The effect of bufalin in HCT-116 and SW620 colon cancer cells was detected by assessing cell viability and cell death...
February 19, 2019: Drug and Chemical Toxicology
Yu-Jin Tang, Kai Li, Cheng-Liang Yang, Ke Huang, Jing Zhou, Yu Shi, Ke-Gong Xie, Jia Liu
Background: Spinal cord injury (SCI) is a disease of the central nervous system with few restorative treatments. Autophagy has been regarded as a promising therapeutic target for SCI. The inhibitor of phosphatase and tensin homolog deleted on chromosome ten (PTEN) bisperoxovanadium (bpV[pic]) had been claimed to provide a neuroprotective effect on SCI; but the underlying mechanism is still not fully understood. Materials and methods: Acute SCI model were generated with SD Rats and were treated with control, acellular spinal cord scaffolds (ASC) obtained from normal rats, bpV(pic), and combined material of ASC and bpV(pic)...
2019: Drug Design, Development and Therapy
Lin Du, Cheng-Fu Tan, Chao Wang, Wei Zhang, Ya-Ni Tang, Mei-Lin Chen, Wei-Wei Liu, Jiao-Lan Li
OBJECTIVE: To observe the effect of "Neiguan" (PC6)-electroacupuncture (EA) or moxibustion (Moxi) pretreatment on myocardial apoptosis and expression of autophagy related proteins light chain (LC) 3-Ⅰ and LC3-Ⅱ in rats with myocardial ischemia/reperfusion injury (MIRI), so as to explore their mechanisms underlying improvement of MIRI. METHODS: Forty SD rats (half male and half female) were randomly divided into sham operation, model, ischemic preconditioning (IP), EA and Moxi groups ( n =8 in each group)...
January 25, 2019: Zhen Ci Yan Jiu, Acupuncture Research
Rastislav Horos, Magdalena Büscher, Rozemarijn Kleinendorst, Anne-Marie Alleaume, Abul K Tarafder, Thomas Schwarzl, Dmytro Dziuba, Christian Tischer, Elisabeth M Zielonka, Asli Adak, Alfredo Castello, Wolfgang Huber, Carsten Sachse, Matthias W Hentze
Vault RNAs (vtRNA) are small non-coding RNAs transcribed by RNA polymerase III found in many eukaryotes. Although they have been linked to drug resistance, apoptosis, and viral replication, their molecular functions remain unclear. Here, we show that vault RNAs directly bind the autophagy receptor sequestosome-1/p62 in human and murine cells. Overexpression of human vtRNA1-1 inhibits, while its antisense LNA-mediated knockdown enhances p62-dependent autophagy. Starvation of cells reduces the steady-state and p62-bound levels of vault RNA1-1 and induces autophagy...
February 12, 2019: Cell
Li Dong, Boris Reljic, Jen G Cheung, Elizabeth S Ng, Lisa M Lindqvist, Andrew G Elefanty, David L Vaux, Hoanh Tran
Withdrawal of the growth factor interleukin-3 (IL-3) from IL-3-dependent myeloid cells causes them to undergo Bax/Bak1-dependent apoptosis, whereas factor-deprived Bax-/- Bak1-/- cells remain viable, but arrest and shrink. It was reported that withdrawal of IL-3 from Bax-/- Bak1-/- cells caused decreased expression of the glucose transporter Glut1, leading to reduced glucose uptake, so that arrested cells required Atg5-dependent autophagy for long-term survival. In other cell types, a decrease in Glut1 is mediated by the thioredoxin-interacting protein (Txnip), which is induced in IL-3-dependent myeloid cells when growth factor is removed...
February 15, 2019: Cell Death and Differentiation
Vijay Pancholi
In the past decade, the field of the cellular microbiology of group A Streptococcus ( S. pyogenes ) infection has made tremendous advances and touched upon several important aspects of pathogenesis, including receptor biology, invasive and evasive phenomena, inflammasome activation, strain-specific autophagic bacterial killing, and virulence factor-mediated programmed cell death. The noteworthy aspect of S. pyogenes -mediated cell signaling is the recognition of the role of M protein in a variety of signaling events, starting with the targeting of specific receptors on the cell surface and on through the induction and evasion of NETosis, inflammasome, and autophagy/xenophagy to pyroptosis and apoptosis...
January 2019: Microbiology Spectrum
Yin Cao, Qinglin Li, Lulu Liu, Hui Wu, Fei Huang, Changhong Wang, Yunyi Lan, Fang Zheng, Faping Xing, Qiang Zhou, Qi Li, Hailian Shi, Beibei Zhang, Zhengtao Wang, Xiaojun Wu
BACKGROUND AND PURPOSE: Sleep deprivation (SD) compromises learning and memory in both humans and animals, which can be reversed by administration of modafinil, a wake-promoting drug. Dysfunctional autophagy promotes the activation of apoptotic cascades, ultimately leading to an increased neuronal death, which can be alleviated by autophagy inhibitors. This study is aimed to investigate the alleviative effect and mechanism of modafinil on the excessive autophagy in hippocampus of mice with deficiency of learning and memory induced by SD...
February 14, 2019: British Journal of Pharmacology
Shuqiang Chen, Guoqiang Dong, Shanchao Wu, Na Liu, Wannian Zhang, Chunquan Sheng
Natural product evodiamine and its derivatives represent a promising class of multi-target antitumor agents. However, the clinical development of these compounds has been hampered by a poor understanding of their antitumor mechanisms. To tackle this obstacle, herein, novel fluorescent probes were designed to elucidate the antitumor mode of action of 10-hydroxyevodiamine. This compound was proven to be distributed in the mitochondria and lysosomes and to act by autophagy and apoptosis mechanisms.
January 2019: Acta Pharmaceutica Sinica. B
Johanna Magga, Laura Vainio, Teemu Kilpiö, Juha J Hulmi, Saija Taponen, Ruizhu Lin, Markus Räsänen, Zoltán Szabó, Erhe Gao, Lea Rahtu-Korpela, Tarja Alakoski, Johanna Ulvila, Mika Laitinen, Arja Pasternack, Walter J Koch, Kari Alitalo, Riikka Kivelä, Olli Ritvos, Risto Kerkelä
Activin A and myostatin, members of the transforming growth factor (TGF)-β superfamily of secreted factors, are potent negative regulators of muscle growth, but their contribution to myocardial ischemia-reperfusion (IR) injury is not known. The aim of this study was to investigate if activin 2B (ACVR2B) receptor ligands contribute to myocardial IR injury. Mice were treated with soluble ACVR2B decoy receptor (ACVR2B-Fc) and subjected to myocardial ischemia followed by reperfusion for 6 or 24 h. Systemic blockade of ACVR2B ligands by ACVR2B-Fc was protective against cardiac IR injury, as evidenced by reduced infarcted area, apoptosis, and autophagy and better preserved LV systolic function following IR...
January 24, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
Alfredo Cruz-Gregorio, Imelda Martínez-Ramírez, José Pedraza-Chaverri, Marcela Lizano
Head and neck cancer (HNC) is the sixth cause of cancer-related death worldwide. Head and neck squamous cells carcinoma (HNSCC) is the most frequent subtype of HNC. The development of HNSCC is associated to alcohol consumption, smoking or infection by high-risk human Papillomavirus (HR-HPV). Although the incidence of cancers associated with alcohol and tobacco has diminished, HNSCC associated with HR-HPV has significantly increased in recent years. However, HPV-positive HNSCC responds well to treatment, which includes surgery followed by radiation or chemoradiation therapy...
February 5, 2019: Cancers
Majid Sharifi, Sara Haji Hosseinali, Ali Akbar Saboury, Eva Szegezdi, Mojtaba Falahati
With the expansion of the field of nanomedicine, the use of nanomaterials in cancer treatment has raised questions about their safety and unpredictable adverse effects. To date, the hazardous effects of nanomaterials have been investigated based on cell survival and cellular functionality, such as membrane integrity, mitochondrial activity and cell morphology. It is increasingly noted that more detailed analysis of regulated cell death pathways (RCD) triggered by nanomaterials is essential to understand their full mechanism of action...
February 11, 2019: Journal of Controlled Release: Official Journal of the Controlled Release Society
Maryam Sulaiman Alsaadi
DAPK (death-associated protein kinase) is a calcium/calmodulin (Ca2+/CaM) regulated serine/threonine kinase. Structurally, it assumes a multi-domain structure and participates in various apoptotic systems which imply that it may interact with a wide range of intracellular components to exert its action. DAPK plays vital roles in pro-apoptotic, apoptotic and autophagic pathways. In addition, it plays important roles in many diseases such as cancer, Alzheimer's disease, cerebral ischemia and epilepsy. Although a novel protein, DAPK's various cellular signal transduction pathways proves that it can be a target for a potential future therapeutic effects...
February 11, 2019: International Journal of Developmental Neuroscience
Chengmin Xuan, Yong Gao, Mingwei Jin, Shumei Xu, Lei Wang, Yuan Wang, Rui Han, Kunpeng Shi, Xincheng Chen, Qi An
The ubiquitin-proteasome system is the primary cellular pathway for protein degradation, mediating 80% of intracellular protein degradation. Because of the widespread presence of ubiquitin-modified protein substrates, ubiquitination can regulate a variety of cellular activities including cell proliferation, apoptosis, autophagy, endocytosis, DNA damage repair, and immune responses. With the continuous generation of genomics data in recent years it has become particularly important to analyze these data effectively and reasonably...
February 14, 2019: IUBMB Life
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