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Survivin, apoptosis

Chao Wu, Liguang Mao, Xie Huang, Weitao Fu, Xiong Cai, Yuepiao Cai, Liqun Shen, Xiaoxia Ye
Survivin is the smallest member of IAP (inhibitor of apoptosis protein) family, which plays important roles in both mitosis and apoptosis. It has become an attractive drug target due to its overexpression in many human cancers. Survivin has been proven to bind to Smac/DIABLO protein that indirectly inhibits apoptosis. Meanwhile, it is the key subunit of chromosome passenger complex (CPC) which bind to the N-terminal tail of phosphorylated histone H3T3ph during mitosis. Up to now, Survivin directly targeting inhibitor has yet to merge since the difficulty of disrupting the protein-protein interactions (PPIs) between Survivin and its substrate proteins...
May 8, 2018: Journal of Molecular Graphics & Modelling
Y X Zhao, D Luo, Y H Zhang, B Shen, B X Wang, Z F Sun
Objective: The aim of this study is to investigate the inhibitory effect and mechanism of tanshinone ⅡA combined with cisplatin on tumor Fadu cells in pharyngeal squamous cell carcinoma. Method: Cytotoxicity was determined by CCK8 assay. Flow cytometry was used to detect apoptosis and cell cycle distribution. Western blotting was used to assess the protein expression of related signaling proteins. Result: Compared with the two single drug groups treated with Tan ⅡA and DDP respectively, the combination group showed significantly higher anti-proliferative rate ( P <0...
May 20, 2017: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
Qiong Cheng, Juan Du, Lin Xie, Xiao Liu, Zheng Li, Fuguo Zuo, Jinfeng Wu, Jinhua Xu
SOX4 (SRY Box 4) has attracted attention due to its important effects on cell growth, proliferation and apoptosis, among other cellular processes. However, the role of SOX4 in melanoma cell apoptosis remains unclear. In the present study, we investigated whether inhibition of SOX4 induces melanoma cell apoptosis, and explored the possible mechanism involving the NF-κB signaling pathway. SOX4 was knocked down using a lentivirus in melanoma A2058 and SK-MEL-5 cell lines. Cell proliferation was measured by MTT assay...
May 16, 2018: Oncology Reports
Fang Qiu, Xia Zhao
The aim of the present study was to investigate the influence of liposome‑plasmid encoding mutant survivin‑T34A (PST34A) on tumor growth in cervical cancer in vivo. Liposome‑plasmid DNA encoding mutant survivin‑T34A was constructed and administered via an intraperitoneal injection in mice inoculated with cervical cancer cells. Following the establishment of the tumor model, the animals were randomly divided into four groups: i) The normal saline group (NS; 100 µl sterile saline once/3 days for 15 days); ii) the 1,2‑dioleoyl‑3‑trimethylammonium‑propane (DOTAP) control (100 µg DOTAP once/3 days for 15 days); iii) the plasmid PST34A (10 µg PST34A once/3 days for 15 days); and iv) the PST34A+DOTAP (10 µg PST34A+100 µg DOTAP once/3 days for 15 days)...
May 11, 2018: Molecular Medicine Reports
Bo Wang, Shuangshuang Han
Apoptosis contributes to the pathogenesis of traumatic brain injury (TBI). Engineered exosomes incorporated with therapeutic nuclear acids have been explored for gene therapy for human diseases. The current study sought to investigate the effect of modified exosome-containing plasmids expressing B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X-protein (Bax) shRNA on apoptosis and neural functions after TBI. C57BL/6J mice were subjected to controlled cortical impact injury and were treated with the modified exosomes...
May 11, 2018: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Hisako Ono, Yoshihiro Sowa, Mano Horinaka, Yosuke Iizumi, Motoki Watanabe, Mie Morita, Emi Nishimoto, Tetsuya Taguchi, Toshiyuki Sakai
PURPOSE: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Eribulin was approved for the treatment of metastatic breast cancer through the EMBRACE trial, and a subgroup analysis in this clinical trial indicated the efficacy of eribulin in patients with TNBC. However, the prognosis of patients with TNBC is still poor due to various molecular characteristics. Therefore, there is an urgent need for a more effective treatment for the management of TNBC...
May 11, 2018: Breast Cancer Research and Treatment
Selvi Kunnimalaiyaan, Victoriana K Schwartz, Iris Alao Jackson, T Clark Gamblin, Muthusamy Kunnimalaiyaan
BACKGROUND: Neuroblastoma (NB) is a devastating disease. Despite recent advances in the treatment of NB, about 60% of high-risk NB will have relapse and therefore long-term event free survival is very minimal. We have reported that targeting glycogen synthase kinase-3 (GSK-3) may be a potential strategy to treat NB. Consequently, investigating LY2090314, a clinically relevant GSK-3 inhibitor, on NB cellular proliferation and may be beneficial for NB treatment. METHODS: The effect of LY2090314 was compared with a previously studied GSK-3 inhibitor, Tideglusib...
May 11, 2018: BMC Cancer
Yan Wang, Jian Zhong, Jiaojiao Bai, Rongsheng Tonga, Feifei An, Pengcheng Jiao, Lin He, Daiwen Zeng, Enwu Long, Junfeng Yan, Jiying Yu, Lulu Cai
Apoptosis is one of the pathways of programmed cell death (PCD), which leads to pathognomic cellular changes different from cellular necrosis. It includes the death receptor pathway and the mitochondrial pathway, both of which involve many key proteins, including cytochrome c, Fas, the Bcl-2 family, caspases, survivin and p53. In apoptosis-related diseases, such as cancer, many proteins associated with apoptosis are abnormally expressed. The majority of anti-cancer agents promote apoptosis to induce cancer cell death...
May 11, 2018: Current Drug Metabolism
Kuo-Sheng Hung, Chung-Chi Hsiao, Tun-Wen Pai, Chin-Hwa Hu, Wen-Shyong Tzou, Wen-Der Wang, Yet-Ran Chen
BACKGROUND: Differential gene expression analysis using RNA-seq data is a popular approach for discovering specific regulation mechanisms under certain environmental settings. Both gene ontology (GO) and KEGG pathway enrichment analysis are major processes for investigating gene groups that participate in common biological responses or possess related functions. However, traditional approaches based on differentially expressed genes only detect a few significant GO terms and pathways, which are frequently insufficient to explain all-inclusive gene regulation mechanisms...
April 24, 2018: BMC Systems Biology
Arfaa Sajid, Qaisar Manzoor, Munawar Iqbal, Amit Kumar Tyagi, Raja Adil Sarfraz, Anam Sajid
The present study was conducted to appraise the anticancer activity of Pinus roxburghii essential oil along with chemical composition evaluation. MTT assay revealed cytotoxicity induction in colon, leukemia, multiple myeloma, pancreatic, head and neck and lung cancer cells exposed to essential oil. Cancer cell death was also observed through live/dead cell viability assay and FACS analysis. Apoptosis induced by essential oil was confirmed by cleavage of PARP and caspase-3 that suppressed the colony-forming ability of tumor cells and 50 % inhibition occurred at a dose of 25 μg/mL...
2018: EXCLI Journal
Ali Hassanzadeh, Majid Farshdousti Hagh, Mohammad Reza Alivand, Ali Akbar Movassaghpour Akbari, Karim Shams Asenjan, Raedeh Saraei, Saeed Solali
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily that induces apoptosis in different types of cancer cells via activation of caspase cascade. TRAIL interacts with its cognate receptors that placed on cancer cells surface, including TRAIL-R1 (death receptor 4, DR4), TRAIL-R2 (death receptor 5, DR5), TRAIL-R3 (decoy receptor 1, DcR1), TRAIL-R4 (decoy receptor 2, DcR2), and osteoprotegerin (OPG). Despite high apoptosis-inducing ability of TRAIL, various cancerous cells gain resistance to TRAIL gradually, and consequently TRAIL potential for apoptosis stimulation in these cells diminishes intensely...
May 9, 2018: Journal of Cellular Physiology
Sabrina Giantulli, Francesca De Iuliis, Ludovica Taglieri, Simone Carradori, Giusi Menichelli, Stefania Morrone, Susanna Scarpa, Ida Silvestri
Tumors are complex and heterogeneous but, despite this, they share the ability to proliferate continuously, irrespective of the presence of growth signals, leading to a higher fraction of actively growing and dividing cells compared with normal tissues. For this reason, the cytotoxic antimitotic treatments remain an important clinical tool for tumors. Among these drugs, antitubulin compounds constitute one of the most effective anticancer chemotherapies; however, they cause dose-limiting side effects. Therefore, it is still necessary to develop compounds with new targets and new mechanisms of action to reduce side effects or chemoresistance...
May 5, 2018: Anti-cancer Drugs
Wei Wang, Bo Zhang, Arul M Mani, Zhongzhi Wu, Yu Fan, Wei Li, Zhao-Hui Wu
Therapeutic resistance developed after chemotherapy and aggressive metastasis are the major causes for cancer-related death in triple negative breast cancer (TNBC) patients. Survivin is the smallest member of Inhibitor-of-Apoptosis Proteins (IAPs) family, which plays critical roles in cell division and cell survival. High expression levels of survivin have been associated with therapeutic resistance in various cancers. We recently developed a novel small molecule survivin inhibitor mimicking IAP-binding motif of second mitochondria-derived activator of caspase, which showed high potency in promoting survivin degradation...
May 7, 2018: Journal of Pharmacology and Experimental Therapeutics
Eun-Ji Kim, Gyeoung-Jin Kang, Jung-Il Kang, Hye-Jin Boo, Jin Won Hyun, Young Sang Koh, Weon-Young Chang, Young Ree Kim, Jung-Mi Kwon, Young Hee Maeng, Eun-Sook Yoo, Chang Hoon Lee, Hee-Kyoung Kang
Here, we investigated whether over-activation of AKT pathway is important in the resistance to 5-fluorouracil (5-FU) in SNU-C5/5-FU cells, 5-FU-resistant human colon cancer cells. When compared to wild type SNU-C5 cells (WT), SNU-C5/5-FU cells showed over-activation of PI3K/AKT pathway, like increased phosphorylation of AKT, mTOR, and GSK-3β, nuclear localization of β-catenin, and decreased E-cadherin. Moreover, E-cadherin level was down-regulated in recurrent colon cancer tissues compared to primary colon cancer tissues...
April 13, 2018: Oncotarget
Q Jin, X H Zhu, C Z Lin, H Zhang, Y W Cao, X Q Ding, Z H Lyu
Objective: To investigate the effects and mechanism of Holothurian Glycosaminoglycan (hGAG) alone in combination with cisplatin (DDP) on apoptosis of pulmonary adenocarcinoma cell A549. Methods: A549 cells were separately treated with blank, hGAG, DDP and hGAG combined with DDP (hGAG + DDP). The cell morphology in 4 groups was observed using light microscope. CCK8 assay was used to determine the cell viability. Flow cytometry by Hoechst 33258 and AnnexinV-FITC/PI staining was applied to detect cell apoptosis...
April 23, 2018: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Toshiyuki Sumi, Sachie Hirai, Miki Yamaguchi, Yusuke Tanaka, Makoto Tada, Toshiro Niki, Hiroki Takahashi, Yuji Sakuma
High expression levels of survivin in KRAS-mutant lung adenocarcinomas are linked with unfavorable patient outcomes, suggesting that survivin is a promising target for tumor treatment. We found that trametinib, a MEK inhibitor, downregulates survivin expression in the RB1-positive KRAS-mutant lung adenocarcinoma cell lines H358 and H441. In these cell lines, trametinib treatment induced p21 expression and dephosphorylated RB1, leading to sustained suppression of survivin. Knockdown of p21 or RB1 restored survivin expression in trametinib-treated cells, at least partially, which supports the contribution of these molecules to trametinib-mediated survivin suppression...
May 1, 2018: Biochemical and Biophysical Research Communications
Dongyu Li, Chenghao Hu, Huibin Li
Survivin, also known as baculoviral inhibitor of apoptosis repeat-containing 5, is a novel member of the inhibitor of apoptosis protein family. Survivin is highly expressed in tumors and embryonic tissues and is associated with tumor cell differentiation, proliferation, invasion and metastasis; however, survivin is expressed at low levels in normal terminally differentiated adult tissues. Meanwhile, the expression level of survivin is also a negative prognostic factor for patients with cancer. These unique characteristics of survivin make it an exciting potential therapeutic target for cancer treatment...
May 2018: Biomedical Reports
Wei-Peng Su, Li-Na Sun, Shun-Liang Yang, Hu Zhao, Teng-Yue Zeng, Wei-Zhen Wu, Dong Wang
Here, we aimed to investigate the carcinogenic effects of apolipoprotein C1 (APOC1) in prostate cancer (PCa). APOC1 expression was evaluated in PCa and normal prostate specimens, and lentivirus-mediated RNA interference was used to knockdown APOC1 in DU145 cells. The effects of APOC1 silencing on cell proliferation, cell cycle arrest, and apoptosis were assessed. APOC1 expression was much higher in PCa tissues than in normal tissues. Moreover, APOC1 silencing inhibited cell proliferation and colony formation, arrested cell cycle progression, and enhanced apoptosis in DU145 cells...
May 2, 2018: Journal of Biochemical and Molecular Toxicology
Jin Chen, Qun Ren, Yuanming Cai, Tingting Lin, Weimin Zuo, Jin Wang, Rong Lin, Ling Zhu, Ping Wang, Huiyue Dong, Hu Zhao, Lianghu Huang, Yunfeng Fu, Shunliang Yang, Jianming Tan, Xiaopeng Lan, Shuiliang Wang
We had previously demonstrated that increased expression of ErbB3 is required for ErbB2-mediated paclitaxel resistance in breast cancer cells. In the present study, we have explored the possible role of mesenchymal stem cells (MSCs) in regulating the paclitaxel-sensitivity of ErbB2/ErbB3-coexpressing breast cancer cells. We show that human umbilical cord-derived MSCs express significantly higher level of neuregulin-1 as compared with ErbB2/ErbB3-coexpressing breast cancer cells themselves. Coculture or treatment with conditioned medium of MSCs not only decreases the anti-proliferation effect of paclitaxel on ErbB2/ErbB3-coexpressing breast cancer cells, but also significantly inhibits paclitaxel-induced apoptosis...
April 28, 2018: Biochemical and Biophysical Research Communications
Madhura Patankar, Sara Väyrynen, Anne Tuomisto, Markus Mäkinen, Sinikka Eskelinen, Tuomo J Karttunen
BACKGROUND/AIM: Micropapillary structures (MIPs) are focal piles of columnar cells without extracellular matrix contact, and common in serrated colorectal carcinoma (CRC). In order to characterize biology of MIPs in colorectal cancer (CRC), the proliferation and apoptosis rates, and survivin expression were compared between MIPs and other cancer epithelial cells of CRC (non-MIPs). MATERIALS AND METHODS: We assessed 46 samples of normal colorectal mucosa, 62 carcinomas and 54 polyps for proliferation (Ki67), apoptosis (M30), and survivin expression by immunohistochemistry...
May 2018: Anticancer Research
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