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Bcl-2 family proteins

Liya Su, Qimuge Suyila, Ling Yang, Hong Li, Yaguang Xi, Xiulan Su
Numerous chemotherapeutic agents promote tumor cell death by activating the intrinsic apoptosis signaling pathway. This pathway is regulated by mitochondrial dysfunction, which occurs through an intricate process controlled by complex interactions between B-cell lymphoma 2 (Bcl-2) family members and other cellular proteins. Bcl-2-associated X protein (Bax) is a proapoptotic protein that is an essential component of the intrinsic apoptosis signaling pathway. Patients lacking Bax may be less sensitive to chemotherapy due to an impaired intrinsic apoptosis signaling pathway...
October 2017: Experimental and Therapeutic Medicine
Bo Tang, Aoshuang Xu, Jian Xu, Haifan Huang, Lei Chen, Yan Su, Lannan Zhang, Junying Li, Fengjuan Fan, Jun Deng, Liang Tang, Chunyan Sun, Yu Hu
Chromosome 17p deletions are present in 10% of patients with newly diagnosed multiple myeloma (MM), and are associated with inferior prognosis. miR-324-5p is located on chromosome 17p, and shows diverse functions in different types of cancers. However, its role in MM is largely unknown. Here we found the expression of miR-324-5p was decreased in MM, especially in del(17p) MM. In contrast, the expression of Hedgehog (Hh) signaling components was elevated, indicating a correlation between miR-324-5p and Hh signaling in MM...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
Tahsin F Kellici, Maria V Chatziathanasiadou, Min-Sung Lee, Nisar Sayyad, Elena G Geromichalou, Eirinaios I Vrettos, Antonis D Tsiailanis, Seung-Wook Chi, George D Geromichalos, Thomas Mavromoustakos, Andreas G Tzakos
Anti-apoptotic proteins, like the Bcl-2 family proteins, present an important therapeutic cancer drug target. Their activity is orchestrated through neutralization upon interaction of pro-apoptotic protein counterparts that leads to immortality of cancer cells. Therefore, generating compounds targeting these proteins is of immense therapeutic importance. Herein, Induced Fit Docking (IFD) and Molecular Dynamics (MD) simulations were performed to rationally design quercetin analogues that bind in the BH3 site of the Bcl-xL protein...
September 13, 2017: Organic & Biomolecular Chemistry
Feng Tang, Shengjun Tang, Xiaolong Guo, Chao Yang, Ke Jia
The aim of the present study was to investigate the role of the cancer‑testis antigen family 45 member A1 (CT45A1) in the proliferation, apoptosis, invasion and metastasis of lung cancer cells, and the associated molecular mechanisms. Western blotting determined that the expression of CT45A1 in normal lung cells was far lower than that observed in lung cancer cells. Following the transfection of CT45A1 small (or short) interfering (si)RNA and its negative control into A549 cells using Lipofectamine 2000, the CT45A1 protein and mRNA levels were determined further by western blotting and reverse transcription‑polymerase chain reaction...
September 12, 2017: Molecular Medicine Reports
Mohammad Abid, Yogesh A Sonawane, Jacob I Contreras, Sandeep Rana, Amarnath Natarajan
BACKGROUND: Anti-apoptotic members of the Bcl-2 family of proteins are upregulated in a majority of cancers and are potential therapeutic targets. Fragment-based design led to the development of clinical candidates that target Bcl-xL/Bcl-2. Although these Bcl-xL/Bcl-2 inhibitors showed promise in pre-clinical studies, resistance was observed to several Bcl-xL inhibitors, when used alone. This has been attributed to the over-expression of Mcl-1, another member of the Bcl-2 family of proteins...
September 11, 2017: Current Medicinal Chemistry
Yu-Ting Tseng, Yuh-Jyh Jong, Wei-Fang Liang, Fang-Rong Chang, Yi-Ching Lo
BACKGROUND: Deficiency of survival motor neuron (SMN) protein, which is encoded by the SMN1 and SMN2 genes, induces widespread splicing defects mainly in spinal motor neurons, and leads to spinal muscular atrophy (SMA). Currently, there is no effective treatment for SMA. Liuwei dihuang (LWDH), a traditional Chinese herbal formula, possesses multiple therapeutic benefits against various diseases via modulation of the nervous, immune and endocrine systems. Previously, we demonstrated water extract of LWDH (LWDH-WE) protects dopaminergic neurons and improves motor activity in models of Parkinson's disease...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ameesha Tomar, Swati Vasisth, Sana Irfan Khan, Salma Malik, Tapas Chandra Nag, Dharamveer Singh Arya, Jagriti Bhatia
BACKGROUND AND PURPOSE: Cisplatin is a widely used chemotherapeutic agent but now-a-days its usage is limited in clinical chemotherapy because of its severe nephrotoxic effect on renal tissues. Galangin, a flavonoid obtained from ginger family has been demonstrated to have antioxidant, anti-apoptotic and anti-inflammatory properties. This study is aimed to investigate the possible ameliorative effect of galangin in a rodent model of cisplatin-induced nephrotoxicity. MATERIAL AND METHODS: Adult male albino wistar rats were divided into six groups (n=6) viz normal, cisplatin-control, galangin (25, 50 and 100mg/kg p...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Mahmut Sözmen, Alparslan K Devrim, Yonca B Kabak, Tuba Devrim, Mert Sudagidan
Periostin is an extracellular matrix protein from fasciclin family, and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The present study was designed to investigate cardioprotective effects of the recombinant murine periostin peptide administration in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague Dawley rats in 4 groups (n = 21): control group (1), periostin-treated group (2), ISO-treated group (3), and ISO + periostin-treated group (4)...
September 11, 2017: Cardiovascular Toxicology
Dharmasivam Mahendiran, Raju Senthil Kumar, Vijayan Viswanathan, Devadasan Velmurugan, Aziz Kalilur Rahiman
The bis(4'-(4-tolyl)-2,2':6',2″-terpyridine)copper(II) complex [Cu(ttpy)2]Cl2 was synthesized and authenticated by single crystal analysis, which shows distorted octahedral geometry around copper(II) ion. The crystal packing is stabilized by C-H···π inter and intramolecular interactions. The complex was found to be lipophilic as determined by shake-flask method. In vitro cytotoxicity of the complex was tested against Ehrlich ascites carcinoma (EAC) and L6 myotube cell lines. The complex exhibit potent cytotoxicity with respect to the commercially available anticancer drug cisplatin...
September 7, 2017: Journal of Biological Inorganic Chemistry: JBIC
Matthias Kollek, Gesina Voigt, Christian Molnar, Fabronia Murad, Daniela Bertele, Christopher Felix Krombholz, Sheila Bohler, Verena Labi, Stefan Schiller, Mirjam Kunze, Stephan Geley, Charlotte M Niemeyer, Ana Garcia-Saez, Miriam Erlacher
During hematopoietic stem cell transplantation, a substantial number of donor cells are lost because of apoptotic cell death. Transplantation-associated apoptosis is mediated mainly by the proapoptotic BCL-2 family proteins BIM and BMF, and their proapoptotic function is conserved between mouse and human stem and progenitor cells. Permanent inhibition of apoptosis in donor cells caused by the loss of these BH3-only proteins improves transplantation outcome, but recipients might be exposed to increased risk of lymphomagenesis or autoimmunity...
September 7, 2017: Journal of Experimental Medicine
Lilly Magdalena WeiΔ, Manuela Hugle, Simone Fulda
In this study, we investigated the molecular mechanisms of eribulin-induced cell death and its therapeutic potential in combination with the PLK1 inhibitor BI 6727 in Ewing sarcoma (ES). Here, we show that eribulin triggers cell death in a dose-dependent manner in a panel of ES cell lines. In addition, eribulin at subtoxic, low nanomolar concentrations acts in concert with BI 6727 to induce cell death and to suppress long-term clonogenic survival. Mechanistic studies reveal that eribulin monotherapy at cytotoxic concentrations and co-treatment with eribulin at subtoxic concentrations together with BI 6727 arrest cells in the M phase of the cell cycle prior to the onset of cell death...
August 8, 2017: Oncotarget
George M Burslem, Hannah F Kyle, Adam Nelson, Thomas A Edwards, Andrew J Wilson
The modulation of protein-protein interactions (PPIs) represents a major challenge in modern chemical biology. Current approaches (e.g. high-throughput screening, computer aided ligand design) are recognised as having limitations in terms of identification of hit matter. Considerable success has been achieved in terms of developing new approaches to PPI modulator discovery using the p53/hDM2 and Bcl-2 family of PPIs. However these important targets in oncology might be considered as "low-hanging-fruit". Hypoxia inducible factor (HIF) is an emerging, but not yet fully validated target for cancer chemotherapy...
June 1, 2017: Chemical Science
Bo Wook Kim, Hanbyoul Cho, Kris Ylaya, Haruhisa Kitano, Joon-Yong Chung, Stephen M Hewitt, Jae-Hoon Kim
BACKGROUND/AIM: Bcl-2-like protein 11 (BIM) is a pro-apoptotic member of the Bcl-2 protein family. BIM elicits cell death by binding to pro-survival Bcl-2 proteins. Even though the association of BIM expression with cell death has been investigated, its clinical survival significance in cervical cancer has not. In the current study, the prognostic significance of BIM in cervical cancer was investigated. PATIENTS AND METHODS: The study included normal cervical tissues (n=254), cervical intraepithelial neoplasia (CIN) tissues (n=275), and invasive cervical cancer (n=164)...
September 2017: Anticancer Research
Tomoya Takenaka, Miku Katayama, Ayaka Sugiyama, Masaya Hagiwara, Ikuo Fujii, Tomoka Takatani-Nakase, Susumu S Kobayashi, Ikuhiko Nakase
BACKGROUND/AIM: Gefitinib is a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and has been approved for the treatment of non-small cell lung cancers (NSCLCs) with EGFR mutations. Here we demonstrated that gefitinib induced a significantly enhanced biological activity of succinate-tetrazolium reductase (STR) in mitochondria and mitochondrial membrane potential in HCC827 cells (EGFR mutation NSCLCs, sensitive to gefitinib) at a high cell density. MATERIALS AND METHODS: We assessed the biological activity (STR, mitochondrial membrane potential, expression level of Bcl-2 family proteins) of gefitinib on NSCLCs at different cell densities...
September 2017: Anticancer Research
Philipp Wolf
Despite improved diagnostic and therapeutic intervention, advanced prostate cancer (PC) remains incurable. The acquired resistance of PC cells to current treatment protocols has been traced to apoptosis resistance based on the upregulation of anti-apoptotic proteins of the Bcl-2 family. The use of BH3 mimetics, mimicking pro-apoptotic activator or sensitizer proteins of the intrinsic apoptotic pathway, is therefore a promising treatment strategy. The present review gives an overview of preclinical and clinical studies with pan- and specific BH3 mimetics as sensitizers for cell death and gives an outlook how they could be effectively used for the therapy of advanced PC in future...
2017: Frontiers in Pharmacology
Yao Liu, Zhi-Hong Zong, Xue Guan, Li-Li Wang, Yang Zhao
OBJECTIVES: Ovarian carcinoma is one of the highest incidence of tumors in women, and the generation, development and prognosis of epithelial ovarian carcinoma (EOC) remains an open field of study. The role of long non-coding RNAs (lncRNAs) in epithelial ovarian carcinoma is an emerging area of research. MATERIALS AND METHODS: LncRNA PCA3 expression was determined in EOC and normal ovarian tissues by RT-PCR. Phenotypes indicative of tumor progression and aggressiveness, including cell proliferation, migration, invasion, and expression of related molecules, were analysed in EOC cell following knockdown of lncRNA PCA3 by transfection with small interfering RNA (siRNA)...
August 29, 2017: Gene
Min-Jung Kang, Hye Hyeon Yun, Jeong-Hwa Lee
The Bcl-2 family protein, Mcl-1 is known to have anti-apoptotic functions, and depletion of Mcl-1 by cellular stresses favors the apoptotic process. Moreover, Mcl-1 levels are frequently increased in various cancer cells, including non-small cell lung cancer (NSCLC), and is implicated in resistance to conventional chemotherapy and in cancer metastasis. In this study, we demonstrated that KRIBB11 accelerates the proteasomal degradation of Mcl-1 in the NSCLC cell line, A549. While KRIBB11 is an inhibitor of HSF1, we found that KRIBB11 induced Mcl-1 degradation in an HSF1-independent manner...
August 29, 2017: Biochemical and Biophysical Research Communications
P Polčic, M Mentel, G Gavurníková, I Bhatia-Kiššová
Apoptosis, an intrinsic cellular pathway that eliminates unwanted cells from multicellular organisms, represents an important mechanism for protection against viral infections. When cells infected by viruses get recognized by immune cells, apoptosis is triggered in the infected cells. Among the many regulators of apoptosis involved in this process, a family of proteins homologous to oncogene Bcl-2 plays a central role. Their concerted activities converge to permeabilization of mitochondrial membranes and activation of apoptotic pathways in the presence of diverse apoptotic signals, including virus infection...
2017: Acta Virologica
Saiyang Zhang, Tingyu Li, Li Zhang, Xiangyu Wang, Hangqi Dong, Lili Li, Dongjun Fu, Yongchun Li, Xiaolin Zi, Hong-Min Liu, Yanbing Zhang, Hongde Xu, Cheng-Yun Jin
A new series of etherification chalcone derivatives were designed and synthesized through Willimison etherification and Claisen-Schmidt condensation. Among them, compound 2-c which was given chemical name of S17, has been successfully screened out as the most potent one on gastric cancer cell line(MGC803) through the investigation for their effects against the growth of five cancer cell lines (EC109, HepG2, MCF7, MGC803, SKNSH). S17 exhibited strong anti-proliferative activity on other two gastric cancer cells (HGC27 and SGC7901), but less cytotoxicity to non-malignant gastric epithelial cells GES1...
August 29, 2017: Scientific Reports
Zia Ur Rehman, Tesfaye Worku, John S Davis, Hira Sajjad Talpur, Dinesh Bhattarai, Ishwari Kadariya, HuaGua Hua, Jing Cao, Rahim Dad, Farmanullah, Tarique Hussain, Liguo Yang
Sertoli cells produce anti-Müllerian hormone (AMH), a glycoprotein belonging to the transforming growth factor-beta family. AMH mediates the regression of Müllerian ducts in the developing male fetus. However, the role of AMH in the regulation of primary Sertoli cells remains unclear. The present study was designed to investigate the effect of AMH on the viability and proliferation of Sertoli cells, with an additional focus on stem cell factor (SCF). Treatment of Sertoli cells with increasing concentrations of rh-AMH (0, 10, 50, 100, and 800ng/ml) for two days revealed that AMH, at high concentrations, increased apoptosis...
August 26, 2017: Journal of Steroid Biochemistry and Molecular Biology
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