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Chloroquine and cancer

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https://www.readbyqxmd.com/read/29780826/silibinin-induced-human-glioblastoma-cell-apoptosis-concomitant-with-autophagy-through-simultaneous-inhibition-of-mtor-and-yap
#1
Zhuan-Li Bai, Vincent Tay, Shu-Zhong Guo, Juan Ren, Mao-Guo Shu
Silibinin, also known as silybin, is the major flavonolignan isolated from Silybum marianum . Although previous reports demonstrated that silibinin exhibits significant tumor suppressor activities in various cancers by promoting cell apoptosis, it was also shown to trigger autophagy to counteract apoptosis induced by exogenous stresses in several types of cells. However, there is no report to address the role of silibinin induced autophagy in human A172 and SR glioblastoma cells. Our study showed that silibinin treatment not only inhibited the metabolic activities of glioblastoma cells but also promoted their apoptosis through the regulation of caspase 3 and PARP-1 in concentration- and time-dependent manners...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29777783/accelerated-lipid-catabolism-and-autophagy-are-cancer-survival-mechanisms-under-inhibited-glutaminolysis
#2
Anna Halama, Michal Kulinski, Shaima S Dib, Shaza B Zaghlool, Kodappully S Siveen, Ahmad Iskandarani, Jonas Zierer, Kirti S Prabhu, Noothan J Satheesh, Aditya M Bhagwat, Shahab Uddin, Gabi Kastenmüller, Olivier Elemento, Steven S Gross, Karsten Suhre
Suppressing glutaminolysis does not always induce cancer cell death in glutamine dependent tumors because cells may switch to alternative energy sources. To reveal compensatory metabolic pathways, we investigated the metabolome-wide cellular response to inhibited glutaminolysis in cancer cells. Glutaminolysis inhibition with C.968 suppressed cell proliferation but was insufficient to induce cancer cell death. We found that lipid catabolism was activated as a compensation for glutaminolysis inhibition. Accelerated lipid catabolism, together with oxidative stress induced by glutaminolysis inhibition, triggered autophagy...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29774126/autophagy-deficient-breast-cancer-shows-early-tumor-recurrence-and-escape-from-dormancy
#3
Hussein F Aqbi, Liliya Tyutyunyk-Massey, Rebecca C Keim, Savannah E Butler, Theresa Thekkudan, Supriya Joshi, Timothy M Smith, Dipankar Bandyopadhyay, Michael O Idowu, Harry D Bear, Kyle K Payne, David A Gewirtz, Masoud H Manjili
Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773091/inactivated-sendai-virus-induces-ros-dependent-apoptosis-and-autophagy-in-human-prostate-cancer-cells
#4
Miao Qian, Hai Ming Tan, Ning Yu, Tao Wang, Quan Zhang
OBJECTIVE: The current study aims to investigate the effect of Hemagglutinating virus of Japan envelope (HVJ-E) on induction of apoptosis and autophagy in human prostate cancer PC3 cells, and the underlying mechanisms. METHODS: PC3 cells were treated with HVJ-E at various multiplicity of infection (MOI), and the generated reactive oxygen species (ROS), cell viability, apoptosis, and autophagy were detected, respectively. Next, the role of ROS played in the regulation of HVJ-E-induced apoptosis and autuphagy in PC3 cells were analysed...
April 2018: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/29749472/insufficient-radiofrequency-ablation-promotes-hepatocellular-carcinoma-cell-progression-via-autophagy-and-the-cd133-feedback-loop
#5
Xiaofei Wang, Qingsong Deng, Kai Feng, Shihan Chen, Jiayun Jiang, Feng Xia, Kuansheng Ma, Ping Bie
Insufficient radiofrequency ablation (iRFA) often leads to residual hepatocellular carcinoma (HCC) progression. However, the mechanism is still poorly understood. In the present study, we demonstrated that LC3B protein expression levels were significantly increased in the residual hepatocellular carcinoma cells after radiofrequency ablation (RFA) treatment in vivo. Moreover, iRFA promoted autophagy, autophagosome formation and autophagic flux in Huh-7 and SMMC7721 cell lines in vitro. In addition, iRFA induced HCC cell viability and invasion...
April 26, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29725750/characterization-of-the-endolysosomal-system-in-human-chordoma-cell-lines-is-there-a-role-of-lysosomes-in-chemoresistance-of-this-rare-bone-tumor
#6
Dagmar Kolb-Lenz, Robert Fuchs, Birgit Lohberger, Ellen Heitzer, Katharina Meditz, Dominique Pernitsch, Elisabeth Pritz, Andrea Groselj-Strele, Andreas Leithner, Bernadette Liegl-Atzwanger, Beate Rinner
Chordoma is a rare tumor of the bone derived from remnants of the notochord with pronounced chemoresistance. A common feature of the notochord and chordoma cells is distinct vacuolization. Recently, the notochord vacuole was described as a lysosome-related organelle. Since lysosomes are considered as mediators of drug resistance in cancer, we were interested whether they may also play a role in chemoresistance of chordoma. We characterized the lysosomal compartment in chordoma cell lines by cytochemistry, electron microscopy (ELMI) and mutational analysis of genes essential for the physiology of lysosomes...
May 3, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29723445/basal-level-of-autophagy-and-map1lc3b-ii-as-potential-biomarkers-for-dha-induced-cytotoxicity-in-colorectal-cancer-cells
#7
Helle Samdal, Malin A Sandmoe, Lene C Olsen, Elaf A H Jarallah, Therese S Høiem, Svanhild A Schønberg, Caroline H H Pettersen
The omega-3 fatty acid docosahexaenoic acid (DHA) is known as an anticancer agent. Colorectal cancer cells (CRCs) exhibit different sensitivity towards DHA, but the mechanisms involved are still unclear. Gene expression profiling of ten CRC cell lines demonstrated a correlation between the level of DHA sensitivity and different biological stress responses, like endoplasmic reticulum (ER) stress, oxidative stress and autophagy. The basal level of autophagy and MAP1LC3B-II protein correlated with DHA sensitivity in the cell lines studied...
May 3, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29719377/attenuation-of-everolimus-induced-cytotoxicity-by-a-protective-autophagic-pathway-involving-erk-activation-in-renal-cell-carcinoma-cells
#8
Yizhou Zeng, Xiaofang Tian, Quan Wang, Weiyang He, Jing Fan, Xin Gou
Aim: The mammalian target of rapamycin (mTOR) pathway is a critical target for cancer treatment and the mTOR inhibitor everolimus (RAD001) has been approved for treatment of renal cell carcinoma (RCC). However, the limited efficacy of RAD001 has led to the development of drug resistance. Autophagy is closely related to cell survival and death, which may be activated under RAD001 stimulation. The aim of the present study was to identify the underlying mechanisms of RAD001 resistance in RCC cells through cytoprotective autophagy involving activation of the extracellular signal-regulated kinase (ERK) pathway...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29713246/autophagy-inhibition-improves-the-cytotoxic-effects-of-receptor-tyrosine-kinase-inhibitors
#9
Sanja Aveic, Marcella Pantile, Pierfrancesco Polo, Viktoryia Sidarovich, Marilena De Mariano, Alessandro Quattrone, Luca Longo, Gian Paolo Tonini
Background: A growing field of evidence suggests the involvement of oncogenic receptor tyrosine kinases (RTKs) in cell transformation. Deregulated activity of RTKs in tumors can determine disease progression and therapeutic responses in several types of cancer, including neuroblastoma (NB). Therefore, RTKs targeting is a worthwhile challenge for the oncologists. Nevertheless, acquired resistance to RTK inhibitors (RTKi) remains a serious problem. Autophagy activation is among the possible obstacles for good efficacy of the therapy with RTKi...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29708817/montelukast-inhibits-hypoxia-inducible-factor-1%C3%AE-translation-in-prostate-cancer-cells
#10
Caixia Tang, Hu Lei, Jinfu Zhang, Meng Liu, Jin, Hao Luo, Hanzhang Xu, Yingli Wu
Through regulating the expression of hundreds of genes, hypoxia-inducible factor -1(HIF-1) plays a critical role in hypoxic adaption of cancer cells and is considered as a target for cancer therapy. Here we show that montelukast, a clinical leukotriene receptor antagonist for the treatment of asthma, inhibits hypoxia or CoCl2 -induced HIF-1α activation and reduces its protein expression in prostate cancer cells. However, the other two leukotriene receptor antagonists, pranlukast and zafirlukast, cannot decrease HIF-1α protein, which indicates that montelukast-induced downregulation of HIF-1α is not mediated by leukotriene receptor...
April 30, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29700990/promise-of-chemokine-network-targeted-nanoparticles-in-combination-nucleic-acid-therapies-of-metastatic-cancer
#11
REVIEW
Ying Xie, Yazhe Wang, Jing Li, Yu Hang, David Oupický
Chemokines and chemokine receptors play key roles in cancer progression and metastasis. Although multiple chemokines and chemokine receptors have been investigated, inhibition of CXCR4 emerged as one of the most promising approaches in combination cancer therapy, especially when focused on the metastatic disease. Small RNA molecules, such as small interfering RNA (siRNA) and microRNA (miRNA), represent new class of therapeutics for cancer treatment through RNA interference-mediated gene silencing. However, the clinical applicability of siRNA and miRNA is severely limited by the lack of effective delivery systems...
April 26, 2018: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/29699632/mulberry-anthocyanins-improves-thyroid-cancer-progression-mainly-by-inducing-apoptosis-and-autophagy-cell-death
#12
Hou-Long Long, Feng-Feng Zhang, Hong-Ling Wang, Wen-Shi Yang, Hai-Tao Hou, Jing-Kui Yu, Bin Liu
Dietary anthocyanin compounds have multiple biological effects, including antioxidant, anti-inflammatory, and anti-atherosclerotic characteristics. The present study evaluated the anti-tumor capacity of mulberry anthocyanins (MA) in thyroid cancer cells. Our data showed that MA suppressed SW1736 and HTh-7 cell proliferation in a time- and dose-dependent manner. Meanwhile, flow cytometry results indicated that MA significantly increased SW1736 and HTh-7 cell apoptosis. We additionally observed that SW1736 and HTh-7 cell autophagy was markedly enhanced after MA treatment...
May 2018: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/29684045/autophagic-flux-blockage-by-accumulation-of-weakly-basic-tenovins-leads-to-elimination-of-b-raf-mutant-tumour-cells-that-survive-vemurafenib
#13
Marcus J G W Ladds, Andrés Pastor-Fernández, Gergana Popova, Ingeborg M M van Leeuwen, Kai Er Eng, Catherine J Drummond, Lars Johansson, Richard Svensson, Nicholas J Westwood, Anna R McCarthy, Fredrik Tholander, Mihaela Popa, David P Lane, Emmet McCormack, Gerald M McInerney, Ravi Bhatia, Sonia Laín
Tenovin-6 is the most studied member of a family of small molecules with antitumour activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these molecules...
2018: PloS One
https://www.readbyqxmd.com/read/29670691/combined-acylselenourea-diselenide-structures-new-potent-and-selective-antitumoral-agents-as-autophagy-activators
#14
Pablo Garnica, Ignacio Encío, Daniel Plano, Juan A Palop, Carmen Sanmartín
A series of 16 new diselenide-acylselenourea conjugates have been designed following the fragment-based drug strategy. Compound in vitro cytotoxic potential was evaluated against six human cancer cell lines and two nonmalignant derived cell lines with the aim of determining their potency and selectivity. Nine derivatives exhibited GI50 values under 10 μM in at least four cancer cell lines. A clear gap situated phenyl substitution over heterocyclic moieties in terms of selectivity. Among carbocyclic compounds, derivatives 2 and 7 significantly inhibited cell growth of breast adenocarcinoma cells with GI50 values of 1...
April 12, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29670359/d-limonene-exhibits-antitumor-activity-by-inducing-autophagy-and-apoptosis-in-lung-cancer
#15
Xiao Yu, Hongyan Lin, Yu Wang, Wenwen Lv, Shuo Zhang, Ying Qian, Xiaobei Deng, Nannan Feng, Herbert Yu, Biyun Qian
Purpose: d-limonene is a plant extract with widespread application, and it has been recently reported to have antiproliferative and proapoptotic effects on cancer cells. However, the mechanisms by which d-limonene achieves these effects, especially in lung cancer, are not entirely clear. Therefore, the goal of this study was to examine the effects of d-limonene on lung cancer and explore its mechanisms of action. Methods: We examined the therapeutic effects of d-limonene on lung cancer cells and in a xenograft animal model by characterizing its effects on the pathways of apoptosis and autophagy...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29665004/thiostrepton-degrades-mutant-p53-by-eliciting-an-autophagic-response-in-sw480-cells
#16
Dhanya Kalathil, Manu Prasad, Maharrish Chelladurai, Samu John, Asha S Nair
Mutations in p53 gene are one of the hallmarks of tumor development. Specific targeting of mutant p53 protein has a promising role in cancer therapeutics. Our preliminary observation showed destabilization of mutant p53 protein in SW480, MiaPaCa and MDAMB231 cell lines upon thiostrepton treatment. In order to elucidate the mechanism of thiostrepton triggered mutant p53 degradation, we explored the impact of proteasome inhibition on activation of autophagy. Combined treatment of thiostrepton and cycloheximide/chloroquine prevented the degradation of mutant p53 protein, reinforcing autophagy as the means of mutant p53 destabilization...
April 17, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29658606/chloroquine-inhibits-cell-growth-in-human-a549-lung-cancer-cells-by-blocking-autophagy-and-inducing-mitochondrial%C3%A2-mediated-apoptosis
#17
Likun Liu, Cuicui Han, Haitao Yu, Wenbin Zhu, Hongxia Cui, Lihong Zheng, Chunjing Zhang, Liling Yue
Chloroquine (CQ) has been revealed to exhibit antitumor activity in several human tumors including lung cancer as mono‑ or add‑on therapy. The antitumor effect of CQ appears to depend on the tumor type, stage and genetic context. Few studies have focused on the mechanism concerning the antitumor effect of CQ monotherapy and the cause and effect relationship among autophagy, apoptosis and CQ in human lung A549 cells. Therefore, the present study aimed to identify the antitumor effect of CQ monotherapy and analyze the possible mechanism...
April 12, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29658588/autophagy-inhibition-potentiates-saha%C3%A2-mediated-apoptosis-in-glioblastoma-cells-by-accumulation-of-damaged-mitochondria
#18
Kovooru Lohitesh, Heena Saini, Abhilasha Srivastava, Sudeshna Mukherjee, Aniruddha Roy, Rajdeep Chowdhury
Glioblastoma multiforme (GBM), often referred to as a grade IV astrocytoma, is the most invasive type of tumor arising from glial cells. The main treatment options for GBM include surgery, radiation and chemotherapy. However, these treatments tend to be only palliative rather than curative. Poor prognosis of GBM is due to its marked resistance to standard therapy. Currently, temozolomide (TMZ), an alkylating agent is used for treatment of GBM. However, GBM cells can repair TMZ‑induced DNA damage and therefore diminish the therapeutic efficacy of TMZ...
April 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29649567/nrf2-signaling-and-autophagy-are-complementary-in-protecting-breast-cancer-cells-during-glucose-deprivation
#19
Alyssa Walker, Anju Singh, Ellen Tully, Juhyung Woo, Anne Le, Tu Nguyen, Shyam Biswal, Dipali Sharma, Edward Gabrielson
Autophagy can serve as a mechanism for survival of cells during nutrient deprivation by recycling cellular macromolecules and organelles transiently to provide essential metabolic substrates. However, autophagy itself causes metabolic stress to cells, and other cellular protective mechanisms likely cooperate with autophagy to promote cell survival during nutrient deprivation. In this study, we explored protective mechanisms in breast cancer cells in the setting of glucose deprivation. While breast cancer cells (MCF7 and T47D) survive in glucose-free medium for three days or more, autophagy is induced in this setting...
April 9, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29649478/autophagy-alteration-prevents-primary-cilium-disassembly-in-rpe1-cells
#20
Yunash Maharjan, Joon No Lee, SeongAe Kwak, Hyewon Lim, Raghbendra Kumar Dutta, Zhi-Qiang Liu, Hong-Seob So, Raekil Park
Primary cilium is a microtubule structure that emanates from the surface of most human cells. Primary cilia assemble during the resting stage (G0 phase) and disassemble with cell cycle progression. Defects associated with the control of the assembly or disassembly of the primary cilium have been implicated in various human diseases, including ciliopathy and cancer. Although studies have suggested the interplay between activation of autophagy and ciliogenesis, any direct mechanism between autophagy abatement and disassembly of primary cilium remains elusive...
April 9, 2018: Biochemical and Biophysical Research Communications
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