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Chloroquine and cancer

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https://www.readbyqxmd.com/read/28208617/inhibition-of-autophagy-by-deguelin-sensitizes-pancreatic-cancer-cells-to-doxorubicin
#1
Xiao Dong Xu, Yan Zhao, Min Zhang, Rui Zhi He, Xiu Hui Shi, Xing Jun Guo, Cheng Jian Shi, Feng Peng, Min Wang, Min Shen, Xin Wang, Xu Li, Ren Yi Qin
Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28199887/killing-colon-cancer-cells-through-pcd-pathways-by-a-novel-hyaluronic-acid-modified-shell-core-nanoparticle-loaded-with-rip3-in-combination-with-chloroquine
#2
Xueyan Hou, Chengli Yang, Lijing Zhang, Tingting Hu, Dan Sun, Hua Cao, Fan Yang, Gang Guo, Changyang Gong, Xiaoning Zhang, Aiping Tong, Rui Li, Yu Zheng
Due to extensive apoptosis defects and multidrug resistance, there is great interest regarding non-apoptotic programmed cell death (PCD) pathways, such as lysosomal-mediated programmed cell death (LM-PCD), necroptosis and autophagy. Because there is an intricate effector network among these PCD pathways, it is expected that they may act synergistically in cancer therapy. In this study, chloroquine (CQ) was found to significantly upregulate receptor-interacting protein kinase 3 (RIP3) expression, and RIP3 were involved in CQ-related autophagy...
January 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28197638/cobalt-chloride-treatment-induces-autophagic-apoptosis-in-human-glioma-cells-via-a-p53-dependent-pathway
#3
Bor-Chin Cheng, Jui-Tai Chen, Shun-Tai Yang, Chung-Ching Chio, Shing-Hwa Liu, Ruei-Ming Chen
Malignant glioma is the most aggressive brain tumor. Hypoxic condition has been explored for killing cancer stem cells or drug-resistant tumor cells. This study investigated the effects of hypoxia on autophagic death and the possible mechanisms. Exposure of human malignant glioma U87-MG cells to cobalt chloride (CoCl2) increased cellular hypoxia-inducible factor-1α levels and concurrently decreased cell viability concentration- and time-dependently. In parallel, treatment with CoCl2 suppressed proliferation of human U87-MG cells...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28176967/parthenolide-suppresses-pancreatic-cell-growth-by-autophagy-mediated-apoptosis
#4
Weifeng Liu, Xinshuai Wang, Junjun Sun, Yanhui Yang, Wensheng Li, Junxin Song
Pancreatic cancer is an aggressive malignancy and is unresponsive to conventional chemotherapies. Parthenolide, a sesquiterpene lactone isolated from feverfew, has exhibited potent anticancer effects against various cancers. The purpose of this report was to investigate the effect and underlying mechanism of parthenolide in human pancreatic cancer Panc-1 and BxPC3 cells. The results demonstrated that parthenolide suppressed the growth and induced apoptosis of Panc-1 and BxPC3 pancreatic cancer cells with the half maximal inhibitory concentration (IC50) ranging between 7 and 9 μM after 24 h of treatment...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28165387/concurrent-autophagy-inhibition-overcomes-the-resistance-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-human-bladder-cancer-cells
#5
Minyong Kang, Kyoung-Hwa Lee, Hye Sun Lee, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim, Ja Hyeon Ku
Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR) inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1), chloroquine (CQ) and 3-methyladenine (3-MA) were used as the pharmacologic inhibitors of autophagy activities...
February 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28158287/the-apoptotic-effect-of-1-s-1-acetoxychavicol-acetate-aca-enhanced-by-inhibition-of-non-canonical-autophagy-in-human-non-small-cell-lung-cancer-cells
#6
Sophia P M Sok, Norhafiza M Arshad, Mohamad Nurul Azmi, Khalijah Awang, Bulent Ozpolat, Noor Hasima Nagoor
Autophagy plays a role in deciding the fate of cells by inducing either survival or death. 1'S-1-acetoxychavicol acetate (ACA) is a phenylpropanoid isolated from rhizomes of Alpinia conchigera and has been reported previously on its apoptotic effects on various cancers. However, the effect of ACA on autophagy remains ambiguous. The aims of this study were to investigate the autophagy-inducing ability of ACA in human non-small cell lung cancer (NSCLC), and to determine its role as pro-survival or pro-death mechanism...
2017: PloS One
https://www.readbyqxmd.com/read/28131902/cq-synergistically-sensitizes-human-colorectal-cancer-cells-to-sn-38-cpt-11-through-lysosomal-and-mitochondrial-apoptotic-pathway-via-p53-ros-cross-talk
#7
Pinjia Chen, Xiaoyong Luo, Peipei Nie, Baoyan Wu, Wei Xu, Xinpeng Shi, Haocai Chang, Bing Li, Xiurong Yu, Zhengzhi Zou
Autophagy plays a key role in supporting cell survival against chemotherapy-induced apoptosis. In this study, we found the chemotherapy agent SN-38 induced autophagy in colorectal cancer (CRC) cells. However, inhibition of autophagy using a small molecular inhibitor 3-methyladenine (3-MA) and ATG5 siRNA did not increase SN-38-induced cytotoxicity in CRC cells. Notably, another autophagy inhibitor chloroquine (CQ) synergistically enhanced the anti-tumor activity of SN-38 in CRC cells with wild type (WT) p53...
January 25, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28131096/tp53inp2-related-basal-autophagy-is-involved-in-the-growth-and-malignant-progression-in-human-liposarcoma-cells
#8
Yamei Hu, Xin Li, Wenwen Xue, Juan Pang, Yiwei Meng, Yan Shen, Qiang Xu
BACKGROUND: Understanding the function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancers. Here, we studied the contribution of basal autophagy in human liposarcoma. METHODS: The levels of basal autophagy were analyzed by measuring autophagy-related protein expression and autophagosome formation. TP53INP2 expression was determined by real-time PCR, western blot and tissue microarray...
January 25, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28127343/in-vitro-antiplasmodial-activity-and-cytotoxic-effect-of-z-2-benzylidene-4-6-dimethoxybenzofuran-3-2h-one-derivatives
#9
Ali Ramazani, Reza Hamidnezhad, Alireza Foroumadi, Seyed Abbas Mirzaei, Somayyeh Maddahi, Seyed Mehdi Hassanzadeh
BACKGROUND: Aurones are naturally occurring compounds that belong to flavenoids family and have antiplasmodial effects. This study investigated some new aurones derivatives against chloroquine sensitive Plasmodium falciparum. Here we report the synthesis, in vitro antiplasmodial activity and cytotoxic evaluation of 11 compound from derivatives of (Z)-2- benzylidene-4, 6-dimethoxybenzofuran-3(2H)-one. METHODS: The cytotoxic evaluations of active compounds were performed with MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide) assay on human breast cancer cell lines; MCF7 and T47D...
July 2016: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/28126348/autophagy-is-required-for-activation-of-pancreatic-stellate-cells-associated-with-pancreatic-cancer-progression-and-promotes-growth-of-pancreatic-tumors-in-mice
#10
Sho Endo, Kohei Nakata, Kenoki Ohuchida, Shin Takesue, Hiromichi Nakayama, Toshiya Abe, Kazuhiro Koikawa, Takashi Okumura, Masafumi Sada, Kohei Horioka, Biao Zheng, Yusuke Mizuuchi, Chika Iwamoto, Masaharu Murata, Taiki Moriyama, Yoshihiro Miyasaka, Takao Ohtsuka, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura
BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) change from a quiescent to activated state in the tumor environment and secrete extracellular matrix (ECM) molecules and cytokines to increase the aggressiveness of tumors. However, it is not clear how PSCs are activated to produce these factors, or whether this process can be inhibited. PSCs have morphological and functional similarities to hepatic stellate cells, which undergo autophagy to promote fibrosis and tumor growth. We investigated whether autophagy activates PSCs, which promotes development of the tumor stroma and growth of pancreatic tumors in mice...
January 23, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28094001/autophagy-inhibition-overcomes-multiple-mechanisms-of-resistance-to-braf-inhibition-in-brain-tumors
#11
Jean M Mulcahy Levy, Shadi Zahedi, Andrea M Griesinger, Andrew Morin, Kurtis D Davies, Dara L Aisner, B K Kleinschmidt-DeMasters, Brent E Fitzwalter, Megan L Goodall, Jacqueline Thorburn, Vladimir Amani, Andrew M Donson, Diane K Birks, David M Mirsky, Todd C Hankinson, Michael H Handler, Adam L Green, Rajeev Vibhakar, Nicholas K Foreman, Andrew Thorburn
Kinase inhibitors are effective cancer therapies, but tumors frequently develop resistance. Current strategies to circumvent resistance target the same or parallel pathways. We report here that targeting a completely different process, autophagy, can overcome multiple BRAF inhibitor resistance mechanisms in brain tumors. BRAF(V600E)mutations occur in many pediatric brain tumors. We previously reported that these tumors are autophagy-dependent and a patient was successfully treated with the autophagy inhibitor chloroquine after failure of the BRAF(V600E) inhibitor vemurafenib, suggesting autophagy inhibition overcame the kinase inhibitor resistance...
January 17, 2017: ELife
https://www.readbyqxmd.com/read/28076793/chloroquine-inducible-par-4-secretion-is-essential-for-tumor-cell-apoptosis-and-inhibition-of-metastasis
#12
Ravshan Burikhanov, Nikhil Hebbar, Sunil K Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S Watt, Danny R Welch, Jodi Maranchie, Akihiro Harada, Vivek M Rangnekar
The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28075474/isomahanine-induces-endoplasmic-reticulum-stress-and-simultaneously-triggers-p38%C3%A2-mapk-mediated-apoptosis-and-autophagy-in-multidrug-resistant-human-oral-squamous-cell-carcinoma-cells
#13
Tanyarath Utaipan, Anan Athipornchai, Apichart Suksamrarn, Surasak Chunsrivirot, Warangkana Chunglok
Advanced oral squamous cell carcinoma (OSCC) is typically aggressive and closely correlated with disease recurrence and poor survival. Multidrug resistance (MDR) is the most critical problem leading to therapeutic failure. Investigation of novel anticancer candidates targeting multidrug-resistant OSCC cells may provide a basis for developing effective strategies for OSCC treatment. In the present study, we investigated the cytotoxic mechanism of a carbazole alkaloid, namely isomahanine, in a multidrug‑resistant OSCC cell line CLS-354/DX...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28070729/inhibiting-autophagy-with-chloroquine-enhances-the-anti-tumor-effect-of-high-let-carbon-ions-via-er-stress-related-apoptosis
#14
Xiaogang Zheng, Xiaodong Jin, Feifei Li, Xiongxiong Liu, Yan Liu, Fei Ye, Ping Li, Ting Zhao, Qiang Li
Energetic carbon ions (CI) offer great advantages over conventional radiations such as X- or γ-rays in cancer radiotherapy. High linear energy transfer (LET) CI can induce both endoplasmic reticulum (ER) stress and autophagy in tumor cells under certain circumstances. The molecular connection between ER stress and autophagy in tumor exposed to high-LET radiation and how these two pathways influence the therapeutic effect against tumor remain poorly understood. In this work, we studied the impact of autophagy and apoptosis induced by ER stress following high-LET CI radiation on the radiosensitivity of S180 cells both in vitro and in vivo...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28042842/novel-2-3-dihydro-1h-pyrrolo-3-2-1-ij-quinazolin-1-ones-synthesis-and-biological-evaluation
#15
Malose J Mphahlele, Tebogo A Khoza, Peaceful Mabeta
Herein we describe the synthesis and evaluation of a series of novel 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones for in vitro cytotoxicity against three human cancer cell lines as well as for potential antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The title compounds were prepared via PdCl₂-mediated endo-dig cyclization of 2-aryl-8-(arylethynyl)-6-bromo-2,3-dihydroquinazolin-4(1H)-ones. The latter were prepared, in turn, via initial Sonogashira cross-coupling of 2-amino-5-bromo-3-iodobenzamide with aryl acetylenes followed by boric acid-mediated cyclocondensation of the intermediate 2-amino-3-(arylethynyl)-5-bromobenzamides with benzaldehyde derivatives...
December 30, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28039459/a-novel-glutaminase-inhibitor-968-inhibits-the-migration-and-proliferation-of-non-small-cell-lung-cancer-cells-by-targeting-egfr-erk-signaling-pathway
#16
Tianyu Han, Meng Guo, Tingting Zhang, Mingxi Gan, Caifeng Xie, Jian-Bin Wang
Metabolic reprogramming is critical for cancer cell proliferation. Glutaminolysis which provides cancer cells with bioenergetics and intermediates for macromolecular synthesis have been intensively studied in recent years. Glutaminase C (GAC) is the first and rate-limiting enzyme in glutaminolysis and plays important roles in cancer initiation and progression. We previously screened a small molecule named 968, a specific inhibitor of GAC, to block the proliferation of human breast cancer cells. In this study, we found that 968 effectively inhibited NSCLC cell proliferation and migration and arrested G0/G1 phase of cell cycle...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031534/autophagy-inhibition-enhances-photocytotoxicity-of-photosan-ii-in-human-colorectal-cancer-cells
#17
Li Xiong, Zhipeng Liu, Guoqing Ouyang, Liangwu Lin, He Huang, Hongxiang Kang, Wei Chen, Xiongying Miao, Yu Wen
Photodynamic therapy (PDT) has emerged as an attractive therapeutic treatment for colorectal cancer because of its accessibility through endoscopy and its ability to selectively target tumors without destroying the anatomical integrity of the colon. We therefore investigated the therapeutic relevance of the interplay between autophagy and apoptosis in Photosan-II (PS-II)-mediated photodynamic therapy (PS-PDT) in in vitro and in vivo models for human colorectal cancer. We observed that PS-PDT-induced dose-dependently triggered apoptosis and autophagy in both SW620 and HCT116 cells...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28029600/therapeutic-targeting-of-autophagy
#18
REVIEW
Christina G Towers, Andrew Thorburn
Autophagy is a catabolic process that facilitates nutrient recycling via degradation of damaged organelles and proteins through lysosomal mediated degradation. Alterations in this complex, and tightly regulated process, lead to disease. Autophagy is widely accepted as cytoprotective against neurodegenerative diseases and a variety of clinical interventions are moving forward to increase autophagy as a therapeutic intervention. Autophagy has both positive and negative roles in cancer and this has led to controversy over whether or how autophagy manipulation should be attempted in cancer therapy...
October 23, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28025112/digestomics-an-emerging-strategy-for-comprehensive-analysis-of-protein-catabolism
#19
REVIEW
Travis S Bingeman, David H Perlman, Douglas G Storey, Ian A Lewis
When cells mobilize nutrients from protein, they generate a fingerprint of peptide fragments that reflects the net action of proteases and the identities of the affected proteins. Analyzing these mixtures falls into a grey area between proteomics and metabolomics that is poorly served by existing technology. Herein, we describe an emerging digestomics strategy that bridges this gap and allows mixtures of proteolytic fragments to be quantitatively mapped with an amino acid level of resolution. We describe recent successes using this technique, including a case where digestomics provided the link between hemoglobin digestion by the malaria parasite and the world-wide distribution of chloroquine resistance...
December 22, 2016: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/27941537/autophagy-inhibitors-chloroquine-and-ly294002-enhance-temozolomide-cytotoxicity-on-cutaneous-melanoma-cell-lines-in-vitro
#20
Oxana O Ryabaya, Andrey N Inshakov, Angelina V Egorova, Marina A Emelyanova, Tatiana V Nasedkina, Alexander S Zasedatelev, Dmitry A Khochenkov, Evgenia V Stepanova
Patients with metastatic melanoma are difficult to treat and have a very poor prognosis because of high resistance to therapy. Recent evidence indicates that tumors could overcome death through autophagy, a survival mechanism, which cancer cells use under lack of energy and nutrient deprivation. Melanoma cells have different sensitivity to temozolomide (TMZ) treatment. In this study, we showed that the combination of autophagy inhibitors chloroquine or LY294002 and TMZ induced enhanced cytotoxicity of alkylating agents on human melanoma cell lines...
March 2017: Anti-cancer Drugs
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