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Chloroquine and cancer

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https://www.readbyqxmd.com/read/29147611/chloroquine-supplementation-increases-the-cytotoxic-effect-of-curcumin-against-her2-neu-overexpressing-breast-cancer-cells-in-vitro-and-in-vivo-in-nude-mice-while-counteracts-it-in-immune-competent-mice
#1
L Masuelli, M Granato, M Benvenuto, R Mattera, R Bernardini, M Mattei, G d'Amati, G D'Orazi, A Faggioni, R Bei, M Cirone
Autophagy is usually a pro-survival mechanism in cancer cells, especially in the course of chemotherapy, thus autophagy inhibition may enhance the chemotherapy-mediated anti-cancer effect. However, since autophagy is strongly involved in the immunogenicity of cell death by promoting ATP release, its inhibition may reduce the immune response against tumors, negatively influencing the overall outcome of chemotherapy. In this study, we evaluated the in vitro and in vivo anti-cancer effect of curcumin (CUR) against Her2/neu overexpressing breast cancer cells (TUBO) in the presence or in the absence of the autophagy inhibitor chloroquine (CQ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29138600/effects-of-chronic-exposure-of-hydroxychloroquine-chloroquine-on-the-risk-of-cancer-metastasis-and-death-a-population-based-cohort-study-on-patients-with-connective-tissue-diseases
#2
L Fardet, I Nazareth, I Petersen
Background: Hydroxychloroquine and chloroquine may reduce the risk of cancer as they inhibit autophagy, in particular, in people with connective tissue diseases. Methods: The hazard ratios of cancers, metastases, and death were assessed in adults with connective tissue diseases prescribed hydroxychloroquine/chloroquine for at least 1 year in comparison with unexposed individuals with the same underlying conditions. A competing risk survival regression analysis was performed...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/29137114/natural-cyclopeptide-ra-xii-a-new-autophagy-inhibitor-suppresses-protective-autophagy-for-enhancing-apoptosis-through-ampk-mtor-p70s6k-pathways-in-hepg2-cells
#3
Lihua Song, Zhe Wang, Yurong Wang, Di Guo, Jianhong Yang, Lijuan Chen, Ninghua Tan
Liver cancer is a progressive, irreversible and aggressive malignant disease, which has no effective chemotherapeutic drugs. RA-XII, a natural cyclopeptide isolated from the traditional Chinese medicine Rubia yunnanensis, exerts anti-cancer and anti-inflammatory activities. This work aimed to investigate the effects of RA-XII on a hepatic tumor and its underlying mechanisms in human hepatoma HepG2 cells. The results showed that RA-XII effectively inhibited the proliferation of HepG2 cells. Consistently, RA-XII significantly induced apoptosis in HepG2 cells by decreasing the expression of caspase 3, 8, 9, and promoting the Cleavage of PARP...
November 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29133031/chloroquine-upregulates-trail-trailr2-expression-and-potentiates-doxorubicin-anti-tumor-activity-in-thioacetamide-induced-hepatocellular-carcinoma-model
#4
Sahar A Helmy, Mohamed El-Mesery, Amro El-Karef, Laila A Eissa, Amal M El Gayar
Impaired apoptosis and systemic toxicity of chemotherapeutic drugs make cancer treatment suboptimal. Thus, there is urgency for drug repurposing which facilitates discovery of safe and effective combination therapy. This study aimed to evaluate chloroquine's (CQ) ability to trigger TRAIL/TRAILR2 apoptotic pathway in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC) either alone or in combination with doxorubicin (DOX). Moreover, its ability to attenuate DOX-induced cardiotoxicity was investigated. TAA was injected in male Sprague Dawely rats (200 mg/kg; ip; 2 times/week) for 16 weeks...
November 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29127189/autophagy-promotes-escape-from-phosphatidylinositol-3-kinase-inhibition-in-estrogen-receptor-positive-breast-cancer
#5
Wei Yang, Sarah R Hosford, Nicole A Traphagen, Kevin Shee, Eugene Demidenko, Stephanie Liu, Todd W Miller
Hyperactivation of the PI3K pathway has been implicated in resistance to antiestrogen therapies in estrogen receptor α (ER)-positive breast cancer, prompting the development of therapeutic strategies to inhibit this pathway. Autophagy has tumor-promoting and -suppressing roles and has been broadly implicated in resistance to anticancer therapies, including antiestrogens. Chloroquine (CQ) is an antimalarial and amebicidal drug that inhibits autophagy in mammalian cells and human tumors. Herein, we observed that CQ inhibited proliferation and autophagy in ER(+) breast cancer cells...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29099265/analysis-of-defective-protein-ubiquitylation-associated-to-adriamycin-resistant-cells
#6
Valérie Lang, Fabienne Aillet, Wendy Xolalpa, Sonia Serna, Laurie Ceccato, Rosa G Lopez-Reyes, Maria Paz Lopez-Mato, Radosław Januchowski, Niels-Christian Reichardt, Manuel S Rodriguez
DNA damage activated by Adriamycin (ADR) promotes ubiquitin-proteasome system-mediated proteolysis by stimulating both the activity of ubiquitylating enzymes and the proteasome. In ADR-resistant breast cancer MCF7 (MCF7(ADR)) cells, protein ubiquitylation is significantly reduced compared to the parental MCF7 cells. Here, we used tandem ubiquitin-binding entities (TUBEs) to analyze the ubiquitylation pattern observed in MCF7 or MCF7(ADR) cells. While in MCF7, the level of total ubiquitylation increased up to six-fold in response to ADR, in MCF7(ADR) cells only a two-fold response was found...
November 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29066501/knockdown-of-brca2-enhances-cisplatin-and-cisplatin-induced-autophagy-in-ovarian-cancer-cells
#7
B Wan, L Dai, L Wang, Y Zhang, H Huang, G Qian, T Yu
Clinical implications of the BRCA2 expression level on treatments of ovarian cancer are controversial. Here we demonstrated that platinum-resistant cancer had a higher percentage of high BRCA2 level (87.5% vs. 43.6%, p = 0.001), and that patients with a low BRCA2 level in cancer tissues had longer progression-free survival (with a median time of 28.0 vs. 12.0 mon, p < 0.001) and platinum-free duration (with a median time of 19.0 vs. 5.0 mon, p < 0.001) compared with those with a high BRCA2 level. In human ovarian cancer cell lines CAOV-3 and ES-2, cisplatin induced an up-regulation of the RAD51 protein, which was inhibited after silencing BRCA2; silencing BRCA2 enhanced the action of cisplatin in vitro and in vivo...
October 24, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29050671/gambogic-acid-improves-non-small-cell-lung-cancer-progression-by-inhibition-of-mtor-signaling-pathway
#8
Teng Zhao, Hong-Jian Wang, Wen-Wen Zhao, Yi-Ling Sun, Li-Kuan Hu
Gambogic acid (GA) has been shown to inhibit cancer cell proliferation, induce apoptosis, and enhance reactive oxygen species accumulation. However, whether GA could improve multidrug resistance through modulating autophagy has never been explored. We demonstrated that the combination of GA and cisplatin (CDDP) resulted in a stronger growth inhibition effect on A549 and NCI-H460 cells using the MTT assay. Furthermore, treatment with GA significantly increased autophagy in these cells. More importantly, GA-induced cell death could be largely abolished by 3-methyladenine (3-MA) or chloroquine (CQ) treatment, suggesting that GA-induced cell death was dependent on autophagy...
November 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/29049999/luteolin-promotes-cell-apoptosis-by-inducing-autophagy-in-hepatocellular-carcinoma
#9
Zhijia Cao, Huainian Zhang, Xiaoyan Cai, Wei Fang, Dong Chai, Ying Wen, Hongsheng Chen, Fujiang Chu, Yongli Zhang
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. Luteolin, a flavonoid from traditional Chinese medicine, shows anti-cancer activity in many cancer cells, including HCC. However, the mechanism underlying the action of luteolin in HCC, especially its role in regulating cell autophagy, remains unclear. In the present study, we investigated the role of luteolin in regulating cell autophagy and the role of autophagy in luteolin-induced apoptosis...
October 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29039550/autophagy-is-essential-for-flavopiridol%C3%A2-induced-cytotoxicity-against-mcf%C3%A2-7-breast-cancer-cells
#10
Shuo Wang, Kai Wang, Huaiquan Wang, Jiankui Han, Hukui Sun
Flavopiridol (FP) exerts antitumoral effects by triggering tumor cell cycle arrest and cytotoxicity in human breast cancer cell lines. The potent antitumor activity of FP is through its inhibition of cyclin‑dependent kinases; however, this may not be the only mechanism of action. The present study aimed to investigate whether FP is able to induce autophagy and to examine the effects of autophagy on cell death in FP‑treated MCF‑7 human breast cancer cells. MCF‑7 cells were treated with either FP alone or FP in combination with chloroquine (CQ)...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29038303/f-actin-reorganization-by-v-atpase-inhibition-in-prostate-cancer
#11
Yamhilette Licon-Munoz, Vera Michel, Colleen A Fordyce, Karlett J Parra
The vacuolar ATPase (V-ATPase) proton pump sustains cellular pH homeostasis, and its inhibition triggers numerous stress responses. However, the cellular mechanisms involved remain largely elusive in cancer cells. We studied V-ATPase in the prostate cancer (PCa) cell line PC-3, which has characteristics of highly metastatic PCa. V-ATPase inhibitors impaired endo-lysosomal pH, vesicle trafficking, migration, and invasion. V-ATPase accrual in the Golgi and recycling endosomes suggests that traffic of internalized membrane vesicles back to the plasma membrane was particularly impaired...
November 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29033794/dihydroartemisinin-exerts-anti-tumor-activity-by-inducing-mitochondrion-and-endoplasmic-reticulum-apoptosis-and-autophagic-cell-death-in-human-glioblastoma-cells
#12
Chengbin Qu, Jun Ma, Xiaobai Liu, Yixue Xue, Jian Zheng, Libo Liu, Jing Liu, Zhen Li, Lei Zhang, Yunhui Liu
Glioblastoma (GBM) is the most advanced and aggressive form of gliomas. Dihydroartemisinin (DHA) has been shown to exhibit anti-tumor activity in various cancer cells. However, the effect and molecular mechanisms underlying its anti-tumor activity in human GBM cells remain to be elucidated. Our results proved that DHA treatment significantly reduced cell viability in a dose- and time-dependent manner by CCK-8 assay. Further investigation identified that the cell viability was rescued by pretreatment either with Z-VAD-FMK, 3-methyladenine (3-MA) or in combination...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29024815/identification-of-a-novel-autophagic-inhibitor-cepharanthine-to-enhance-the-anti-cancer-property-of-dacomitinib-in-non-small-cell%C3%A2-lung-cancer
#13
Zheng-Hai Tang, Wen-Xiang Cao, Xia Guo, Xiao-Yang Dai, Jia-Hong Lu, Xiuping Chen, Hong Zhu, Jin-Jian Lu
Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29022200/high-expression-of-the-mitophagy-related-protein-pink1-is-associated-with-a-poor-response-to-chemotherapy-and-a-poor-prognosis-for-patients-treated-with-neoadjuvant-chemotherapy-for-esophageal-squamous-cell-carcinoma
#14
Kotaro Yamashita, Hiroshi Miyata, Tomoki Makino, Yasunori Masuike, Haruna Furukawa, Koji Tanaka, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Shuji Takiguchi, Eiichi Morii, Masaki Mori, Yuichiro Doki
BACKGROUND: Autophagy plays a major role in cellular homeostasis and is implicated in cancer progression. Damaged mitochondria are scavenged and eliminated by mitochondrial autophagy, referred to as mitophagy, which can promote cancer cell survival. This study investigated the expression and effects of the autophagy-related protein LC3 and the mitophagy-related protein Pink1 in human esophageal squamous cell carcinoma (ESCC). METHODS: Both LC3 and Pink1 were analyzed by immunohistochemistry in tissues from 217 ESCC patients, including 159 patients undergoing neoadjuvant chemotherapy...
October 11, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28987792/cordycepin-induces-apoptotic-cell-death-of-human-brain-cancer-through-the-modulation-of-autophagy
#15
Nipha Chaicharoenaudomrung, Thiranut Jaroonwitchawan, Parinya Noisa
Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health. Cordycepin, extracted from Cordyceps ssp., has been revealed as a strong anticancer agent through several ways; however, the mechanism, by which cordycepin counteracts brain cancers, is still poorly understood. In this study, the underlying mechanisms of cordycepin against human brain cancer cells were explored. SH-SY5Y and U251 cells were being a model to represent human neuroblastoma and glioblastoma, respectively...
October 4, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28981387/aldh1a1-and-hltf-modulate-the-activity-of-lysosomal-autophagy-inhibitors-in-cancer-cells
#16
Shengfu Piao, Rani Ojha, Vito W Rebecca, Arabinda Samanta, Xiao-Hong Ma, Quentin Mcafee, Michael C Nicastri, Meghan Buckley, Eric Brown, Jeffrey D Winkler, Phyllis A Gimotty, Ravi K Amaravadi
Lysosomal autophagy inhibitors (LAI) such as hydroxychloroquine (HCQ) have significant activity in a subset of cancer cell lines. LAIs are being evaluated in cancer clinical trials, but genetic determinants of sensitivity to LAIs are unknown, making it difficult to predict which tumors would be most susceptible. Here we characterize differentially expressed genes in HCQ-sensitive (-S) and -resistant (-R) cancer cells. Notably, expression of canonical macroautophagy/autophagy genes was not associated with sensitivity to HCQ...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28981110/overaccumulation-of-p53-mediated-autophagy-protects-against-betulinic-acid-induced-apoptotic-cell-death-in-colorectal-cancer-cells
#17
Sen Wang, Kexin Wang, Chundong Zhang, Wanfeng Zhang, Qian Xu, Yitao Wang, Yulin Zhang, Yi Li, Ying Zhang, Huifang Zhu, Fangzhou Song, Yunlong Lei, Youquan Bu
Betulinic acid (BA) exhibits cytotoxic activity against some cancer cells. However, the molecular mechanism of BA against CRC cells was little reported. Here, we proved that BA elicited CRC cells' growth inhibition and apoptosis in a dose-dependent manner. In addition, BA treatment induced autophagy via inhibiting the AKT-MTOR signaling pathway. Inhibition of autophagy by either administration of autophagic inhibitor chloroquine or siRNA-mediated knockdown of ATG5 could augment BA-induced apoptotic cell death as well as inhibition of cell proliferation...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28981103/a-novel-acridine-derivative-ls-1-10-inhibits-autophagic-degradation-and-triggers-apoptosis-in-colon-cancer-cells
#18
Wan Fu, Xue Li, Xiaopeng Lu, Luyao Zhang, Ran Li, Nan Zhang, Shan Liu, Xin Yang, Yue Wang, Ying Zhao, Xiangbao Meng, Wei-Guo Zhu
Autophagy promotes cancer cell survival and drug resistance by degrading harmful cellular components and maintaining cellular energy levels. Disruption of autophagy may be a promising approach to sensitize cancer cells to anticancer drugs. The combination of autophagic inhibitors, such as chloroquine (CQ) and lucanthone with conventional cancer therapeutics has been investigated in clinical trials, but adverse drug-drug interactions are a high possibility. Here we designed and synthesized a novel, small-molecule library based on an acridine skeleton and the CQ structure with various modifications and substitutions and screened the compounds for effective autophagy inhibition...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28980060/phase-i-study-of-a-chloroquine-gemcitabine-combination-in-patients-with-metastatic-or-unresectable-pancreatic-cancer
#19
Panagiotis Samaras, Marina Tusup, Thi Dan Linh Nguyen-Kim, Burkhardt Seifert, Helga Bachmann, Roger von Moos, Alexander Knuth, Steve Pascolo
PURPOSE: Following a previously published pre-clinical validation, this phase I study evaluated the safety, maximum tolerated dose, anti-tumour activity and immune status of a gemcitabine-chloroquine combination as a first- or late-line treatment in patients with metastatic or unresectable pancreatic cancer. METHODS: In this 3 + 3 dose escalation study, patients received a single weekly standard dose of intravenous gemcitabine, followed by single weekly oral intake of 100, 200 or 300 mg of chloroquine...
October 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28979680/low-concentration-of-chloroquine-enhanced-efficacy-of-cisplatin-in-the-treatment-of-human-ovarian-cancer-dependent-on-autophagy
#20
Jie Zhu, Ya Zheng, Haiyan Zhang, Jing Zhu, Hong Sun
BACKGROUND: Cisplatin is a common used anti-tumor drug in ovarian cancer therapy with potent effect. Studies have reported that autophagy works as a cell-survival process in cancer, chloroquine has been added to various chemotherapeutic drugs. In the current study, we aim to evaluate whether chloroquine can enhance the effects of cisplatin in treating ovarian cancer. METHODS: CCK-8 assay was used to detect cell viability. Transwell assay was used to examine cell migration and invasion...
2017: American Journal of Translational Research
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