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Drug induced mitochondrial toxicity

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https://www.readbyqxmd.com/read/27913197/doxorubicin-induced-mitophagy-contributes-to-drug-resistance-in-cancer-stem-cells-from-hct8-human-colorectal-cancer-cells
#1
Chen Yan, Lan Luo, Chang-Ying Guo, Shinji Goto, Yoshishige Urata, Jiang-Hua Shao, Tao-Sheng Li
Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133(+)/CD44(+) CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs...
November 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27861613/non-serotonergic-neurotoxicity-by-mdma-ecstasy-in-neurons-derived-from-mouse-p19-embryonal-carcinoma-cells
#2
Dina Popova, Andréas Forsblad, Sanaz Hashemian, Stig O P Jacobsson
3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays...
2016: PloS One
https://www.readbyqxmd.com/read/27859025/modeling-drug-induced-neuropathy-using-human-ipscs-for-predictive-toxicology
#3
Ryo Ohara, Keiko Imamura, Fukiko Morii, Naohiro Egawa, Kayoko Tsukita, Takako Enami, Ran Shibukawa, Toshiki Mizuno, Masanori Nakagawa, Haruhisa Inoue
Drugs under development can cause unpredicted toxicity in humans due to differential drug responsiveness between humans and other disease models, resulting in clinical trial failures. Human induced pluripotent stem cells (iPSCs) are expected to represent a useful tool for toxicity testing. However, among many assays, appropriate cellular assays for predicting neurotoxicity in an iPSC-based model are still uncertain. Here, we generated neurons from iPSCs of Charcot-Marie-Tooth disease (CMT) patients, who are sensitive to anti-cancer drugs and present with the adverse reaction of neuropathy, and analyzed cellular phenotypes...
November 9, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27858292/cisplatin-toxicity-in-dorsal-root-ganglion-neurons-is-relieved-by-meclizine-via-diminution-of-mitochondrial-compromise-and-improved-clearance-of-dna-damage
#4
Murat F Gorgun, Ming Zhuo, Ella W Englander
Chemotherapy-induced neurotoxicity of peripheral nervous system (PNS) hinders efficacy of cancer treatments. Mechanisms initiating PNS injury by anticancer drugs are incompletely understood delaying development of effective management strategies. To understand events triggered in PNS by cancer drugs, we exposed dorsal root ganglion (DRG) neurons to cisplatin, a drug from platinum-based class of chemotherapeutics frequently implicated in peripheral neuropathies. While cisplatin enters cancer cells and forms cisplatin/DNA crosslinks that block cell proliferation, circulating cisplatin can also reach the PNS and produce crosslinks that impede critical DNA transactions in postmitotic neurons...
November 17, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27856111/sensitization-of-cancer-cells-to-cyclophosphamide-therapy-by-an-organoselenium-compound-through-ros-mediated-apoptosis
#5
Pramita Chakraborty, Somnath Singha Roy, Abhishek Basu, Sudin Bhattacharya
Induction of apoptosis has been recognized as an excellent therapeutic approach in cancer. Selenium based compounds are well known for their antitumor and synergistic chemotherapeutic efficacy when combined with a standard antineoplastic drug. Previously, we have reported that an organoselenium compound, diphenylmethyl selenocyanate (DMSE) could effectively protect normal organs and tissues from the toxicity induced by a standard chemotherapeutic drug cyclophosphamide in a tumor bearing mouse model. In this study, as a further step, we have evaluated the effect of DMSE in sensitization of tumor cells to cyclophosphamide-induced cell death...
November 14, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27813185/new-orally-active-dna-minor-groove-binding-small-molecule-ct-1-acts-against-breast-cancer-by-targeting-tumor-dna-damage-leading-to-p53-dependent-apoptosis
#6
Karan Singh Saini, Hamidullah, Raghib Ashraf, Dhanaraju Mandalapu, Sharmistha Das, Mohd Quadir Siddiqui, Sonam Dwivedi, Jayanta Sarkar, Vishnu Lal Sharma, Rituraj Konwar
Targeting tumor DNA damage and p53 pathway is a clinically established strategy in the development of cancer chemotherapeutics. Majority of anti-cancer drugs are delivered through parenteral route for reasons like severe toxicity, lack of stability and poor enteral absorption. Current DNA targeting drugs in clinical like anthracycline suffers from major drawbacks like cardiotoxicity. Here, we report identification of a new orally active small molecule curcumin-triazole conjugate (CT-1) with significant anti-breast cancer activity in vitro and in vivo...
November 4, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27788606/florfenicol-induces-more-severe-hemotoxicity-and-immunotoxicity-than-equal-doses-of-chloramphenicol-and-thiamphenicol-in-kunming-mice
#7
Dongfang Hu, Ziqiang Han, Chunling Li, Lin Lv, Zilong Cheng, Sidang Liu
Amphenicols are effective, broad-spectrum antibiotics that function by inhibiting the peptidyl transferase activity of bacteria, while the drugs can also inhibit mitochondrial protein synthesis in eukaryotes through the same mechanism, which leads to multi-organ toxicity. Some side effects of each drug have been studied, while differences in the severity of the hemotoxicities and immunotoxicities of amphenicols have not been reported. Thus, it is important to identify, evaluate, and compare the potential hemotoxicities and immunotoxicities to guide their proper use in humans and animals, which will guarantee food safety and animal welfare...
October 27, 2016: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/27778023/icariin-protects-against-mpp-induced-neurotoxicity-in-mes23-5-cells
#8
Ai-Li Xu, Ming-Chun Jiang, Xiao-Han Chen, Wen-Fang Chen
Icariin is the major bioactive component of Epimedium and has been demonstrated to be a potential drug for age-related diseases. The present study was aimed to investigate the neuroprotective properties of icariin against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in MES23.5 cells and the possible mechanisms. MTT assay showed that treatment with MPP(+) attenuated the cell viability in a dose-dependent manner in MES23.5 cells. Icariin pretreatment resulted in an enhancement of survival. Immunocytochemistry analysis revealed that icariin treatment attenuated MPP(+)-induced loss of tyrosine hydroxylase (TH) positive cells...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27773706/synthesis-biological-characterization-and-evaluation-of-molecular-mechanisms-of-novel-copper-complexes-as-anticancer-agents
#9
Ceyda Acilan, Buse Cevatemre, Zelal Adiguzel, Didem Karakas, Engin Ulukaya, Nádia Ribeiro, Isabel Correia, João Costa Pessoa
BACKGROUND: To overcome the hurdles of cisplatin, majorly its toxicity and resistance, there has been extensive search for alternative anti-cancer metal-based compounds. Here, three Cu(II)-complexes, Cu(Sal-Gly)(phen), Cu(Sal-Gly)(pheamine), Cu(Sal-Gly)(phepoxy) are characterized for their interaction with DNA, cytotoxicity and mechanism of action. METHODS: The binding ability of the complexes to Calf-Thymus DNA was evaluated by competition fluorescence studies with thiazole-orange, UV-Vis and circular dichroism spectroscopic titrations...
October 20, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27771494/drug-induced-mitochondrial-dysfunction-mechanisms-and-adverse-clinical-consequences
#10
REVIEW
Madhusudanarao Vuda, Ashwin Kamath
Several commonly used medications impair mitochondrial function resulting in adverse effects or toxicities. Drug induced mitochondrial dysfunction may be a consequence of increased production of reactive oxygen species, altered mitochondrial permeability transition, impaired mitochondrial respiration, mitochondrial DNA damage or inhibition of beta-oxidation of fatty acids. The clinical manifestation depends on the specific drug and its effect on mitochondria. Given the ubiquitous presence of mitochondria and its central role in cellular metabolism, drug-mitochondrial interactions may manifest clinically as hepatotoxicity, enteropathy, myelosuppression, lipodystrophy syndrome or neuropsychiatric adverse effects, to name a few...
November 2016: Mitochondrion
https://www.readbyqxmd.com/read/27765658/occupational-exposures-at-a-polyvinyl-chloride-production-facility-are-associated-with-significant-changes-to-the-plasma-metabolome
#11
John J Guardiola, Juliane I Beier, K Cameron Falkner, Benjamin Wheeler, Craig James McClain, Matt Cave
BACKGROUND: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. METHODS: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS(2) analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed...
December 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27761752/a3k2a3-induced-apoptotic-cell-death-of-leishmania-amazonensis-occurs-through-caspase-and-atp-dependent-mitochondrial-dysfunction
#12
Francielle Pelegrin Garcia, Jean Henrique da Silva Rodrigues, Zia Ud Din, Edson Rodrigues-Filho, Tânia Ueda-Nakamura, Rachel Auzély-Velty, Celso Vataru Nakamura
Leishmaniasis is a neglected tropical disease that affects millions of people worldwide. Current therapies mainly rely on antimonial drugs that are inadequate because of their high toxicity and increased drug resistance. An urgent need exists to discover new, more effective, more affordable, and more target-specific drugs. Pathways that are associated with apoptosis-like cell death have been identified in unicellular eukaryotes, including protozoan parasites. In the present study, we studied the mechanism of cell death that is induced by A3K2A3 against L...
October 19, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27748945/survivint34a-increases-the-therapeutic-efficacy-of-arsenic-trioxide-in-mouse-hepatocellular-carcinoma-models
#13
Anliang Huang, Dan Yue, Danying Liao, Liuliu Cheng, Jinhu Ma, Yuquan Wei, Aiping Tong, Ping Cheng
Arsenic trioxide (ATO) has demonstrated clinical efficacy in acute promyelocytic leukemia (APL) and in vitro activity in various solid tumors. As2O3 as single agent exhibits poor efficacy for treatment of hepatocellular carcinoma (HCC) in phase II trial, suggesting that new modalities of treatment with enhanced therapeutic effect and alleviated toxicity are needed for application of As2O3 on patients with HCC. Survivin is the strongest inhibitor of apoptosis protein over-expressed in tumors, which has been proposed as an attractive target for new anticancer interventions...
October 11, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27748578/a-dual-anticancer-efficacy-molecule-a-selective-dark-cytotoxicity-photosensitizer
#14
Jyun-Wei Chen, Cheng-Chung Chang
Unlike traditional binary nanostructures that construct chemotherapy drugs and photodynamic therapy photosensitizers, we introduce a molecule possessing the chemo-photodynamic dual therapy function. A water-soluble aggregation-induced emission enhancement (AIEE) fluorogen, NV-12P, was designed and synthesized based on asymmetric 1, 6-disubstituted naphthalene and can generate particular reactive oxygen species (ROS) to undergo type I photodynamic therapy (PDT) programme under irradiation. Furthermore, this compound can specifically localize in mitochondria and, after biologically evaluation, cause mitochondrial dysfunction and potent cytotoxicity to cancer cells but not normal cells...
October 17, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27744436/pectolinarigenin-suppresses-the-tumor-growth-in-nasopharyngeal-carcinoma
#15
Chengyu Wang, Yin Cheng, Hongyi Liu, Yaping Xu, Hu Peng, Juntian Lang, Jianchun Liao, Haibin Liu, Huanhai Liu, Jingping Fan
BACKGROUND/AIMS: Nasopharyngeal cancer (NPC) is one of the common human malignant diseases all over the world, and chemotherapy remains the main therapy for NPC. However, the survival and life quality of NPC patients are still very poor. Thus, novel and selective anti-tumor agents are pressingly needed. Our previous study identified pectolinarigenin as a novel effective anti-tumor drug candidate for NPC. In this study, we further investigated its anti-tumor activities and explored the potential molecular mechanism...
October 17, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27742868/comparative-renal-safety-assessment-of-the-hepatitis-b-drugs-adefovir-tenofovir-telbivudine-and-entecavir-in-rats
#16
Marianne Uteng, Andreas Mahl, Nicolau Beckmann, Alessandro Piaia, David Ledieu, Valerie Dubost, Elaine Tritto, Armin Wolf, Pierre Moulin, Li Li, Salah-Dine Chibout, Francois Pognan
The aim of this study was to determine the relative safety of four antiviral drugs (telbivudine, tenofovir, adefovir, entecavir) against hepatitis B virus with respect to kidney function and toxicity in male Spraque-Dawley rats. The antiviral drugs were administered once daily for four weeks by oral gavage at about 10 and 25-40 times the human equivalent dose. Main assessments included markers of renal toxicity in urine, magnetic resonance imaging (MRI) of kidney function, histopathology and electron microscopic examination...
October 13, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27715004/biofilm-impeding-agnps-target-skin-carcinoma-by-inducing-mitochondrial-membrane-depolarization-mediated-through-ros-production
#17
Debasis Nayak, Manisha Kumari, Sripathi Rajachandar, Sarbani Ashe, Neethi Chandra Thathapudi, Bismita Nayak
Reactive oxygen species (ROS) are double edged sword that possesses both beneficial and harmful effects. Although basic research on skin cancer prevention has undergone a huge transformation, cases of recurrence with higher rates of drug resistance are some of its drawbacks. Therefore, targeting mitochondria by ROS overproduction provides an alternate approach for anticancer therapy. In the present study green synthesized silver nanoparticles (AgNPs) were explored for triggering the ROS production in A431 skin carcinoma cells...
October 7, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27693243/benzyl-isothiocyanate-promotes-apoptosis-of-oral-cancer-cells-via-an-acute-redox-stress-mediated-dna-damage-response
#18
Yao-Tsung Yeh, Yen-Nien Hsu, Sheng-Yun Huang, Jian-Sheng Lin, Zi-Feng Chen, Nan-Haw Chow, Shu-Hui Su, Huey-Wen Shyu, Ching-Chiang Lin, Wu-Tein Huang, Hua Yeh, Yu-Chia Chih, Yu-Hsuan Huang, Shu-Jem Su
Benzyl isothiocyanate (BITC) is a cruciferous vegetable-derived compound with anticancer properties in human cancer cells. However, its anticancer potential and underlying mechanisms remain absent in human oral cancer cells. Results indicate that BITC inhibits growth, promotes G2/M phase arrest and triggers apoptosis of OC2 cells with a minimal toxicity to normal cells. BITC-induced cell death was completely prevented by pretreatment with thiol-containing redox compounds including N-acetyl-l-cysteine (NAC), glutathione (GSH), dithiothreitol, and 2-mercaptoethanol, but not free radical scavengers mito-TEMPO, catalase, apocynin, l-NAME and mannitol...
September 28, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27689330/interconnections-between-apoptotic-and-autophagic-pathways-during-thiopurine-induced-toxicity-in-cancer-cells-the-role-of-reactive-oxygen-species
#19
Wiem Chaabane, Malin Lindqvist Appell
Thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) are a class of genotoxic drugs extensively used in the treatment of various illnesses including leukemia. Their underlying molecular mechanism of action involves the activation of apoptosis and autophagy but remains widely unclear. Here we present evidence that autophagy induction by thiopurines is a survival mechanism that antagonizes apoptosis and is involved in degrading damaged mitochondria through mitophagy. On the other hand, apoptosis is the main cell death mechanism by thiopurines as its inhibition prohibited cell death...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27666826/systemic-blockade-of-acvr2b-ligands-prevents-chemotherapy-induced-muscle-wasting-by-restoring-muscle-protein-synthesis-without-affecting-oxidative-capacity-or-atrogenes
#20
T A Nissinen, J Degerman, M Räsänen, A R Poikonen, S Koskinen, E Mervaala, A Pasternack, O Ritvos, R Kivelä, J J Hulmi
Doxorubicin is a widely used and effective chemotherapy drug. However, cardiac and skeletal muscle toxicity of doxorubicin limits its use. Inhibiting myostatin/activin signalling can prevent muscle atrophy, but its effects in chemotherapy-induced muscle wasting are unknown. In the present study we investigated the effects of doxorubicin administration alone or combined with activin receptor ligand pathway blockade by soluble activin receptor IIB (sACVR2B-Fc). Doxorubicin administration decreased body mass, muscle size and bone mineral density/content in mice...
September 26, 2016: Scientific Reports
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