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Mitochondria Cancer

Delong Zeng, Jianfu Zhao, Kar-Him Luk, Siu-To Cheung, Ka Hing Wong, Tianfeng Chen
Selenium nanoparticles (SeNPs) are recently emerging as promising anticancer agents because of their high bioavailability, low toxicity and remarkable anticancer activities. However, the effects of surface physicochemical properties on the biological actions remain elusive. Herein we decorated selenium nanoparticles (SeNPs) with various water-soluble polysaccharides extracted from various mushrooms, to compare physical characteristics and anticancer profile of these SeNPs. The results showed that the prepared spherical SeNPs displayed particle sizes at 91-102 nm, and kept stable in aqueous solution for up to 13 weeks...
February 20, 2019: Journal of Agricultural and Food Chemistry
Shuyun Liu, Meng Zhao, Yijie Zhou, Chengshi Wang, Yujia Yuan, Lan Li, William Bresette, Younan Chen, Jingqiu Cheng, Yanrong Lu, Jingping Liu
BACKGROUND: Renal fibrosis is the pathological feature of chronic kidney disease (CKD) which leads to end-stage renal disease (ESRD) and renal failure. Resveratrol [3,5,4'-trihydroxy-trans-stilbene (RSV)] has shown benefits for metabolic diseases and anti-cancer therapy, but its potential risk on renal health has not been fully evaluated. PURPOSE: To investigate the global effects of RSV on renal fibrosis in human tubular epithelial cell (TEC) line HK-2, and in mice with unilateral ureteral obstruction (UUO)...
December 17, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Wei-Liang Sun, Li Wang, Jie Luo, Hua-Wei Zhu, Zheng-Wen Cai
Cancer cells often evade apoptosis induced by anti-cancer drugs, which reduces the efficacy of the drugs. Autophagy/Beclin 1 regulator 1 (Ambra1) is a crucial proautophagic protein. It also plays an important role in the execution of apoptosis. However, the mechanism by which Ambra1 regulates apoptosis has not been fully clarified. Moreover, whether Ambra1 participates in the regulation of paclitaxel-induced apoptosis in breast cancer cells is not clear. Here, we show that Ambra1 inhibits paclitaxel-induced apoptosis in breast cancer cells...
February 20, 2019: Neoplasma
Elena Catanzaro, Francesca Seghetti, Cinzia Calcabrini, Angela Rampa, Silvia Gobbi, Piero Sestili, Eleonora Turrini, Francesca Maffei, Patrizia Hrelia, Alessandra Bisi, Federica Belluti, Carmela Fimognari
Breast cancer is the most diagnosed type of cancer among women for which an exhaustive cure has not been discovered yet. Nowadays, tamoxifen still represents the gold standard for breast cancer therapy; it acts on both estrogen receptor-positive and estrogen receptor-negative breast cancers. Unfortunately, its toxicity and the related chemoresistance undermine its antitumor potential. In this paper, new tamoxifen-based derivatives with a rigid structural motif in their structure were designed, synthesized, and evaluated to assess their antitumor behavior...
February 10, 2019: Bioorganic Chemistry
Kun-Feng Xie, Dong-Dong Guo, Xing-Jing Luo
Mitochondrial Ca2+ uptake, an important governing for Ca2+ homeostasis, is catalyzed by the mitochondrial calcium uniporter (MCU) complex. SMDT1, as a subunit of MCU complex, was essential for bridging the calcium-sensing role of MICU1 and MICU2 with the calcium-conducting role of MCU. However, the molecular mechanism and regulatory purpose of SMDT1 remain largely unexplored, especially no study was reported in cancer. Here, we firstly reported that how SMDT1 exerted its role through mediating mitochondrial dynamic in PDAC malignancy...
February 16, 2019: Biochemical and Biophysical Research Communications
Ningqiang Gong, Xiaowei Ma, Xiaoxia Ye, Qunfang Zhou, Xiaoai Chen, Xiaoli Tan, Shengkun Yao, Shuaidong Huo, Tingbin Zhang, Shizhu Chen, Xucong Teng, Xixue Hu, Jie Yu, Yaling Gan, Huaidong Jiang, Jinghong Li, Xing-Jie Liang
Mitochondrial redox homeostasis, the balance between reactive oxygen species and antioxidants such as glutathione, plays critical roles in many biological processes, including biosynthesis and apoptosis, and thus is a potential target for cancer treatment. Here, we report a mitochondrial oxidative stress amplifier, MitoCAT-g, which consists of carbon-dot-supported atomically dispersed gold (CAT-g) with further surface modifications of triphenylphosphine and cinnamaldehyde. We find that the MitoCAT-g particles specifically target mitochondria and deplete mitochondrial glutathione with atomic economy, thus amplifying the reactive oxygen species damage caused by cinnamaldehyde and finally leading to apoptosis in cancer cells...
February 18, 2019: Nature Nanotechnology
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
Guohai Zhang, Feng'e Ma, Liangping Li, Jingjing Li, Pingping Li, Shulan Zeng, Hongbin Sun, Erguang Li
Palbociclib is a Cdk4/6 inhibitor approved for metastatic estrogen receptor-positive breast cancer. The drug is also under clinical evaluation for metastatic urothelial cancer and other solid tumors. Preclinical studies from multiple tumor types suggest that other factors also affect the sensitivity of individual tumors to Cdk4/6 inhibitor. We show here that Cdk2 has an essential role in palbociclib antitumor effect against bladder cancers. We found that palbociclib induced apoptosis instead of cell cycle arrest to exhibit its anticancer activity in T24 cells, as was evidenced by membrane blebbing, caspase-3 activation and AIF release from mitochondria...
February 14, 2019: Biochemical Pharmacology
Min-Kyue Shin, Jae-Ho Cheong
Metabolic and genotoxic stresses that arise during tumor progression and anti-cancer treatment, respectively, can impose a selective pressure to promote cancer evolution in the tumor microenvironment. This process ultimately selects for the most "fit" clones, which generally have a cancer stem cell like phenotype with features of drug resistance, epithelial-mesenchymal transition, invasiveness, and high metastatic potential. From a bioenergetics perspective, these cancer stem-like cells (CSCs) exhibit mitochondria-centric energy metabolism and are capable of opportunistically utilizing available nutrients such as fatty acids to generate ATP and other metabolic substances, providing a selective advantage for their survival in an impermissible environment and metabolic context...
February 15, 2019: Archives of Pharmacal Research
Teresa Druck, Douglas G Cheung, Dongju Park, Francesco Trapasso, Flavia Pichiorri, Marco Gaspari, Tiziana Palumbo, Rami I Aqeilan, Eugenio Gaudio, Hiroshi Okumura, Rodolfo Iuliano, Cinzia Raso, Kari Green, Kay Huebner, Carlo M Croce
Fhit protein is lost in cancers of most, perhaps all, cancer types; when restored, it can induce apoptosis and suppress tumorigenicity, as shown in vitro and in mouse tumor models in vivo. Following protein cross-linking and proteomics analyses, we characterized a Fhit protein complex involved in triggering Fhit-mediated apoptosis. The complex includes the heat-shock chaperonin pair, HSP60/10, which is likely involved in importing Fhit into the mitochondria, where it interacts with ferredoxin reductase, responsible for transferring electrons from NADPH to cytochrome P450 via ferredoxin, in electron transport chain complex III...
February 15, 2019: Cell Death & Disease
Behnaz Ahangarian Abhari, Nicole McCarthy, Marie Le Berre, Michelle Kilcoyne, Lokesh Joshi, Patrizia Agostinis, Simone Fulda
Since Inhibitor of Apoptosis (IAP) proteins have been implicated in cellular adaptation to endoplasmic reticulum (ER) stress, we investigated the regulation of ER stress-induced apoptosis by small-molecule second mitochondria-derived activator of caspase (Smac) mimetics that antagonize IAP proteins. Here, we discover that Smac mimetic suppresses tunicamycin (TM)-induced apoptosis via resolution of the unfolded protein response (UPR) and ER stress. Smac mimetics such as BV6 selectively inhibit apoptosis triggered by pharmacological or genetic inhibition of protein N-glycosylation using TM or knockdown of DPAGT1, the enzyme that catalyzes the first step of protein N-glycosylation...
February 15, 2019: Cell Death & Disease
Daniel Munro, Cécile Baldy, Matthew E Pamenter, Jason R Treberg
Naked mole-rats (NMRs) are mouse-sized mammals that exhibit an exceptionally long lifespan (>30 vs. <4 years for mice), and resist aging-related pathologies such as cardiovascular and pulmonary diseases, cancer, and neurodegeneration. However, the mechanisms underlying this exceptional longevity and disease resistance remain poorly understood. The oxidative stress theory of aging posits that (a) senescence results from the accumulation of oxidative damage inflicted by reactive oxygen species (ROS) of mitochondrial origin, and (b) mitochondria of long-lived species produce less ROS than do mitochondria of short-lived species...
February 15, 2019: Aging Cell
Satabdi Datta, Diptiman Choudhury, Amlan Das, Dipanwita Das Mukherjee, Moumita Dasgupta, Shreya Bandopadhyay, Gopal Chakrabarti
Paclitaxel is one of the most commonly used drugs for the treatment of nonsmall cell lung cancer (NSCLC). However acquired resistance to paclitaxel, epithelial to mesenchymal transition and cancer stem cell formation are the major obstacles for successful chemotherapy with this drug. Some of the major reasons behind chemoresistance development include increased ability of the cancer cells to survive under stress conditions by autophagy, increased expression of drug efflux pumps, tubulin mutations etc. In this study we found that inhibition of autophagy with chloroquine prevented development of paclitaxel resistance in A549 cells with time and potentiated the effect of paclitaxel by increased accumulation of superoxide-producing damaged mitochondria, with elevated ROS generation, it also increased the apoptotic rate and sub G0/ G1 phase arrest with time in A549 cells treated with paclitaxel and attenuated the metastatic potential and cancer stem cell population of the paclitaxel-resistant cells by ROS mediated modulation of the Wnt/β-catenin signaling pathway, thereby increasing paclitaxel sensitivity...
February 14, 2019: Apoptosis: An International Journal on Programmed Cell Death
Federica Cossu, Mario Milani, Eloise Mastrangelo, Daniele Lecis
Inhibitor of apoptosis (IAP) proteins are characterized by the presence of the conserved baculoviral IAP repeat (BIR) domain that is involved in protein-protein interactions. IAPs were initially thought to be mainly responsible for caspase inhibition, acting as negative regulators of apoptosis, but later works have shown that IAPs also control a plethora of other different cellular pathways. As X-linked IAP (XIAP), and other IAP, levels are often deregulated in cancer cells and have been shown to correlate with patients' prognosis, several approaches have been pursued to inhibit their activity in order to restore apoptosis...
2019: Computational and Structural Biotechnology Journal
Mitsunobu Takeda, Jun Koseki, Hidekazu Takahashi, Norikatsu Miyoshi, Naohiro Nishida, Junichi Nishimura, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Hirofumi Yamamoto, Hideshi Ishii, Yuichiro Doki, Masaki Mori, Naotsugu Haraguchi
Given that cancer stem cells (CSC) play a key role in drug resistance and relapse, targeting CSC remains a promising in cancer therapy. Here we show that RAB5/7, which are involved in the endolysosomal pathway, play key roles in the maintenance of CSC survival via regulation of the mitophagic pathway. Inhibition of RAB5/7 efficiently eliminated colorectal CSC and disrupted cancer foci. In addition, we identified mefloquine hydrochloride, an anti-malarial drug, as a novel RAB5/7 inhibitor and promising colorectal CSC-targeting drug...
February 14, 2019: Cancer Research
Ekaterina S Kharechkina, Anna B Nikiforova, Vera V Teplova, Irina V Odinokova, Olga V Krestinina, Yulia L Baburina, Svetlana A Kruglova, Alexey G Kruglov
BACKGROUND: The opening of the permeability transition pore (PTP) in mitochondria plays a critical role in the pathogenesis of numerous diseases. Mitochondrial matrix pyridine nucleotides are potent regulators of the PTP, but the role of extramitochondrial nucleotides is unclear. METHODS: The PTP opening was explored in isolated mitochondria and mitochondria in permeabilized differentiated and undifferentiated cells in the presence of added NAD(P)(H) in combination with Mg2+ , adenine nucleotides (AN), and the inhibitors of AN translocase (ANT), voltage-dependent anion channel (VDAC), and cyclophilin D...
February 11, 2019: Biochimica et biophysica acta. General subjects
Johannes Klose, Stefan Trefz, Tobias Wagner, Luca Steffen, Arsalie Preißendörfer Charrier, Praveen Radhakrishnan, Claudia Volz, Thomas Schmidt, Alexis Ulrich, Sebastian M Dieter, Claudia Ball, Hanno Glimm, Martin Schneider
OBJECTIVES: Salinomycin is a polyether antibiotic with selective activity against human cancer stem cells. The impact of salinomycin on patient-derived primary human colorectal cancer cells has not been investigated so far. Thus, here we aimed to investigate the activity of salinomycin against tumor initiating cells isolated from patients with colorectal cancer. METHODS: Primary tumor-initiating cells (TIC) isolated from human patients with colorectal liver metastases or from human primary colon carcinoma were exposed to salinomycin and compared to treatment with 5-FU and oxaliplatin...
2019: PloS One
Liwei Ma, Jianwei Wei, Junhu Wan, Weiwei Wang, Li Wang, Yongjie Yuan, Zijun Yang, Xianzhi Liu, Liang Ming
BACKGROUND: Metformin, a first-line drug for type 2 diabetes, could induce apoptosis in cancer cells. However, the concentration of glucose affects the effect of metformin, especially low glucose in the culture medium can enhance the cytotoxicity of metformin on cancer cells. Since mitochondria and endoplasmic reticulum is vital for maintaining cell homeostasis, we speculate that low glucose and metformin-induced cell apoptosis may be associated with mitochondria and endoplasmic reticulum...
February 13, 2019: Journal of Experimental & Clinical Cancer Research: CR
Jian Chen, Hongwei Hou, Huan Chen, Yanbo Luo, Lirong Zhang, Yunfei Zhang, Hansong Liu, Fangfang Zhang, Yong Liu, An Wang, Qingyuan Hu
The incidence of laryngeal cancer (LYC) is second only to lung cancer, which is also the second most common cancer in head and neck cancer. Risk assessment metabolomics biomarkers to diagnose LYC have not been found by now. To profile the metabolites in healthy controls (HCs) and LYC patients (LYCs), urine metabonomics study was performed based on reversed phase liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RPLC-QTOF/MS). Six urine differentially expressed metabolites (Variable Importance in Projection >1, p <  0...
January 30, 2019: Journal of Pharmaceutical and Biomedical Analysis
Douglas R Green
PUMA is a pro-apoptotic Bcl-2 family protein that can act as a tumor suppressor or oncogene in different cancers. In this issue, Kim et al. show that PUMA, independent of its apoptotic function, enforces glycolytic metabolism by inhibiting the transport of pyruvate into the mitochondria, promoting hepatocellular carcinoma.
February 11, 2019: Cancer Cell
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