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Chloroquine and cancer

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https://www.readbyqxmd.com/read/29316551/chloroquine-enhances-the-radiosensitivity-of-bladder-cancer-cells-by-inhibiting-autophagy-and-activating-apoptosis
#1
Feng Wang, Jinyuan Tang, Pengchao Li, Shuhui Si, Hao Yu, Xiao Yang, Jun Tao, Qiang Lv, Min Gu, Haiwei Yang, Zengjun Wang
BACKGROUND/AIMS: Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. METHODS: Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors...
December 22, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29313384/chitosan-nanoparticles-triggered-the-induction-of-ros-mediated-cytoprotective-autophagy-in-cancer-cells
#2
Hao Wang, Xiwei Yu, Chang Su, Yijie Shi, Liang Zhao
There is a close relationship between autophagy and apoptosis during cancer cell death. We used chitosan nanoparticles (CS NPs) to explore the effects of internalized NPs on the induction of autophagy and to confirm the role of autophagic responses elicited by nanomaterials on the tumour cell's fate. CS NPs at nontoxic concentrations ranging from 10-100 μg/mL triggered the induction of autophagy. With the addition of CS NPs, the aggregation of endogenous LC3 was significantly enhanced and acidic autophagic bodies had been accumulated...
January 9, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29285270/metformin-alleviates-nickel-induced-autophagy-and-apoptosis-via-inhibition-of-hexokinase-2-activating-lipocalin-2-in-human-bronchial-epithelial-cells
#3
Yu-Ting Kang, Wen-Cheng Hsu, Chih-Hsien Wu, I-Lun Hsin, Pei-Ru Wu, Kun-Tu Yeh, Jiunn-Liang Ko
Autophagy is an intracellular recycling and degradation process for regulating tumor progression, survival and drug resistance. Nickel compounds have been identified as human carcinogens. However, the role of nickel-induced autophagy in lung carcinogenesis has not yet been fully elucidated. In this study, we determined that hexokinase 2 (HK2), which phosphorylates glucose and regulates autophagy, is the key mediator in nickel-induced autophagy in lung bronchial epithelial cells. We attempted to investigate the effects of the antidiabetic drug metformin on HK2 expression and lung cancer chemoprevention...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29278657/inhibition-of-autophagy-potentiates-the-anti-metastasis-effect-of-phenethyl-isothiocyanate-through-jak2-stat3-pathway-in-lung-cancer-cells
#4
Huimin Wang, Limin Wang, Limin Cao, Qicheng Zhang, Qianqian Song, Zhaowei Meng, Xiang Wu, Ke Xu
Phenethyl isothiocyanate (PEITC) is a natural compound abundant in cruciferous vegetables. PEITC possesses anti-tumor effect in various human malignances. Our previous study has shown that benzyl isothiocyanates (BITC) induce autophagy in lung cancer cells. However, whether autophagy play a role in the inhibitory effect of PEITC on lung cancer metastasis is unclear. In this study, we found that PEITC suppressed migration and invasion of lung cancer cells by regulating MMP2. It also induced autophagy, evidenced by the formation of acidic vesicular organelles (AVOs), the punctate pattern of LC3, the accumulation of LC3-II, and the expression of Beclin-1...
December 26, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29276062/targeting-urothelial-carcinoma-cells-by-combining-cisplatin-with-a-specific-inhibitor-of-the-autophagy-inducing-class-iii-ptdins3k-complex
#5
David Schlütermann, Margaretha A Skowron, Niklas Berleth, Philip Böhler, Jana Deitersen, Fabian Stuhldreier, Nora Wallot-Hieke, Wenxian Wu, Christoph Peter, Michèle J Hoffmann, Günter Niegisch, Björn Stork
BACKGROUND: Cisplatin-based regimens are routinely employed for the treatment of urothelial carcinoma. However, therapeutic success is hampered by the primary presence of or the development of cisplatin resistance. This chemoresistance is executed by multiple cellular pathways. In recent years, the cellular process of autophagy has been identified as a prosurvival pathway of cancer cells. On the one hand, autophagy enables cancer cells to survive conditions of low oxygen or nutrient supply, frequently found in tumors...
December 21, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29258566/5-fu-resistant-emt-like-pancreatic-cancer-cells-are-hypersensitive-to-photochemical-internalization-of-the-novel-endoglin-targeting-immunotoxin-cd105-saporin
#6
Kaja Lund, Cathrine Elisabeth Olsen, Judith Jing Wen Wong, Petter Angell Olsen, Nina Therese Solberg, Anders Høgset, Stefan Krauss, Pål Kristian Selbo
BACKGROUND: Development of resistance to 5-fluorouracil (5-FU) is a major problem in treatment of various cancers including pancreatic cancer. In this study, we reveal important resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma. METHODS: 5-FU resistant (5-FUR), epithelial-to-mesenchymal-like sub-clones of the wild type pancreatic cancer cell line Panc03.27 were previously generated in our lab. We investigated the cytotoxic effect of the endosomal/lysosomal-localizing photosensitizer TPCS2a (fimaporfin) combined with light (photochemical treatment, PCT) using MTS viability assay, and used fluorescence microscopy to show localization of TPCS2a and to investigate the effect of photodamage of lysosomes...
December 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29240252/ganoderma-microsporum-immunomodulatory-protein-induces-apoptosis-and-potentiates-mitomycin-c-induced-apoptosis-in-urinary-bladder-urothelial-carcinoma-cells
#7
Sheng-Yuan Huang, Chih-Cheng Chien, Ruey-Shyang Hseu, Victoria Ying Jen Huang, Shang Ying Chiang, Chi-Jung Huang, Shao-Kuan Chen, Ru-Yin Tsai, Hsi-Ting Lin, Yu-Che Cheng
Current chemotherapy and immunotherapy treatments followed by transurethral resection for urinary bladder urothelial carcinoma (UC) usually suffers from poor prognosis and high recurrence rate. Design and modification of current formulation with the novel adjuvants is needed. A recombinant protein derived from Ganoderma microsporum named as Ganoderma microsporum immunomodulatory protein (GMIP) were used to treat UC cells. We found GMIP elicits a dose-dependent and time-dependent anti-UC cell proliferation effect, with a half-maximal inhibition concentration (IC50 ) comparable to mitomycin C (MMC), a commonly used chemotherapy agent...
December 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29239350/suppression-of-eef-2k-mediated-autophagy-enhances-the-cytotoxicity-of-raddeanin-a-against-human-breast-cancer-cells-in-vitro
#8
Yi-di Guan, Shi-Long Jiang, Pian Yu, Mei Wen, Yi Zhang, Song-Shu Xiao, Xiao-Jun Xu, Yan Cheng
Recent evidence shows that raddeanin A (RA), an oleanane-type triterpenoid saponin extracted from Anemone raddeana Regel, exerts remarkable cytotoxicity against cancer cells in vitro and in vivo. In addition, RA has also been found to activate autophagy in human gastric cancer cells. In this study, we investigated the molecular mechanisms underlying RA-induced autophagy as well as the relationship between RA-induced autophagy and its cytotoxicity in human breast cancer cells in vitro. Treatment with RA (2-8 μmol/L) dose-dependently enhanced autophagy, as evidenced by increased LC3 levels in breast cancer cell lines T47D, MCF-7 and MDA-MB-231...
December 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29225688/repurposing-drugs-in-oncology-redo-chloroquine-and-hydroxychloroquine-as-anti-cancer-agents
#9
Ciska Verbaanderd, Hannelore Maes, Marco B Schaaf, Vikas P Sukhatme, Pan Pantziarka, Vidula Sukhatme, Patrizia Agostinis, Gauthier Bouche
Chloroquine (CQ) and hydroxychloroquine (HCQ) are well-known 4-aminoquinoline antimalarial agents. Scientific evidence also supports the use of CQ and HCQ in the treatment of cancer. Overall, preclinical studies support CQ and HCQ use in anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they are able to sensitise tumour cells to a variety of drugs, potentiating the therapeutic activity. Thus far, clinical results are mostly in favour of the repurposing of CQ. However, over 30 clinical studies are still evaluating the activity of both CQ and HCQ in different cancer types and in combination with various standard treatments...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/29207624/autophagy-suppression-potentiates-the-anti-glioblastoma-effect-of-asparaginase-in-vitro-and-in-vivo
#10
Qicheng Chen, Li Ye, Jiajun Fan, Xuyao Zhang, Huan Wang, Siyang Liao, Ping Song, Ziyu Wang, Shaofei Wang, Yubin Li, Jingyun Luan, Yichen Wang, Wei Chen, Wenjing Zai, Ping Yang, Zhonglian Cao, Dianwen Ju
Asparaginase has been reported to be effective in the treatment of various leukemia and several malignant solid cancers. However, the anti-tumor effect of asparaginase is always restricted due to complicated mechanisms. Herein, we investigated the mechanisms of how glioblastoma resisted asparaginase treatment and reported a novel approach to enhance the anti-glioblastoma effect of asparaginase. We found that asparaginase could induce growth inhibition and caspase-dependent apoptosis in U87MG/U251MG glioblastoma cells...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207150/inhibition-of-autophagy-enhances-the-targeted-therapeutic-effect-of-sorafenib-in-thyroid-cancer
#11
Heqing Yi, Ting Ye, Minghua Ge, Mengdi Yang, Lijun Zhang, Shui Jin, Xuemei Ye, Bin Long, Linfa Li
The multi-target kinase inhibitor sorafenib has been approved for the treatment of patients with advanced differentiated thyroid cancer. However, different sensitivities to sorafenib have been observed, and few patients have benefited from sorafenib treatment in the long term. In the event of acquired resistance to sorafenib it is not beneficial to continue treatment in most patients. Autophagy can be induced in a variety of cancer treatments and plays an important role in cancer treatment. The role of autophagy in sorafenib treatment of thyroid cancer has not been fully demonstrated...
November 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29201061/selective-and-irreversible-induction-of-necroptotic-cell-death-in-lung-tumorspheres-by-short-term-exposure-to-verapamil-in-combination-with-sorafenib
#12
Juan Sebastian Yakisich, Yogesh Kulkarni, Neelam Azad, Anand Krishnan V Iyer
The presence of highly resistant cancer cells and the toxicity to normal cells are key factors that limit chemotherapy. Here, we used two models of highly resistant lung cancer cells: (1) adherent cells growing under prolonged periods of serum starvation (PPSS) and (2) cells growing as floating tumorspheres (FTs) to evaluate the effect of Verapamil (VP) in combination with Sorafenib (SF). Compared to cells growing under routine culture conditions (RCCs), PPPS cells or FTs were highly sensitive to short-term exposure (24 h) to VP 100 μM + SF 5 μM (VP100 + SF5)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29187221/autophagy-maintains-the-stemness-of-ovarian-cancer-stem-cells-by-foxa2
#13
Qiaohua Peng, Jiale Qin, Yanan Zhang, Xiaodong Cheng, Xinyu Wang, Weiguo Lu, Xing Xie, Songfa Zhang
BACKGROUND: Cancer stem cells (CSCs) are regarded as the main cell type responsible for the initiation, metastasis, drug resistance, and recurrence of cancer. But the mechanism by which cancer stem cells maintain their stemness remains unclear. METHODS AND RESULTS: In the present study, ovarian cancer stem cells (OCSCs) were revealed to have an enhanced autophagic flux. Furthermore, their chemoresistance and ability to self-renewal in vitro were decreased when autophagy was inhibited by Bafilomycin A1(BafA1), Chloroquine(CQ) or autophagy related 5(ATG5) knockdown...
November 29, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29171784/necroptosis-promotes-autophagy-dependent-upregulation-of-damp-and-results-in-immunosurveillance
#14
Sheng-Yen Lin, Sung-Yuan Hsieh, Yi-Ting Fan, Wen-Chi Wei, Pei-Wen Hsiao, Dai-Hua Tsai, Tzong-Shoon Wu, Ning-Sun Yang
Programmed necrosis, necroptosis, is considered to be a highly immunogenic activity, often mediated via the release of damage-associated molecular patterns (DAMPs). Interestingly, enhanced macroautophagic/autophagic activity is often found to be accompanied by necroptosis. However, the possible role of autophagy in the immunogenicity of necroptotic death remains largely obscure. In this study, we investigated the possible mechanistic correlation between phytochemical shikonin-induced autophagy and the shikonin-induced necroptosis for tumor immunogenicity...
November 24, 2017: Autophagy
https://www.readbyqxmd.com/read/29163691/autophagy-inhibition-contributes-to-endostar-sensitization-in-esophageal-squamous-cell-carcinoma
#15
Xinghua Han, Zhanggui Wang, Bin Hu, Jianming Xu
Endostar is a novel artificially-synthesized anti-angiogenesis drug, and has been approved for clinical use. Previous studies have indicated that patients with esophageal cancer could benefit from Endostar combined with chemotherapy or chemoradiotherapy. However, the most advantageous use of this drug remains to be elucidated. The role of autophagy in cancer treatment remains controversial. The results of the present study demonstrated that Endostar promotes autophagy activation, which is regulated via phosphorylation inhibition of the downstream signaling molecules of the vascular endothelial growth factor, AKT serine/threonine kinase and mechanistic target of rapamycin signaling pathways...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29162859/ferroquine-the-next-generation-antimalarial-drug-has-antitumor-activity
#16
Artem Kondratskyi, Kateryna Kondratska, Fabien Vanden Abeele, Dmitri Gordienko, Charlotte Dubois, Robert-Allain Toillon, Christian Slomianny, Sébastien Lemière, Philippe Delcourt, Etienne Dewailly, Roman Skryma, Christophe Biot, Natalia Prevarskaya
Despite the tremendous progress in medicine, cancer remains one of the most serious global health problems awaiting new effective therapies. Here we present ferroquine (FQ), the next generation antimalarial drug, as a promising candidate for repositioning as cancer therapeutics. We report that FQ potently inhibits autophagy, perturbs lysosomal function and impairs prostate tumor growth in vivo. We demonstrate that FQ negatively regulates Akt kinase and hypoxia-inducible factor-1α (HIF-1α) and is particularly effective in starved and hypoxic conditions frequently observed in advanced solid cancers...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29160846/a-triphenylphosphonium-functionalized-mitochondriotropic-nanocarrier-for-efficient-co-delivery-of-doxorubicin-and-chloroquine-and-enhanced-antineoplastic-activity
#17
Katerina N Panagiotaki, Zili Sideratou, Spiros A Vlahopoulos, Maria Paravatou-Petsotas, Michael Zachariadis, Nikolas Khoury, Vassilis Zoumpourlis, Dimitris Tsiourvas
Drug delivery systems that target subcellular organelles and, in particular, mitochondria are considered to have great potential in treating disorders that are associated with mitochondrial dysfunction, including cancer or neurodegenerative diseases. To this end, a novel hyperbranched mitochondriotropic nanocarrier was developed for the efficient co-delivery of two different (both in chemical and pharmacological terms) bioactive compounds. The carrier is based on hyperbranched poly(ethyleneimine) functionalized with triphenylphosphonium groups that forms ~100 nm diameter nanoparticles in aqueous media and can encapsulate doxorubicin (DOX), a well-known anti-cancer drug, and chloroquine (CQ), a known chemosensitizer with arising potential in anticancer medication...
November 21, 2017: Pharmaceuticals
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
#18
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
#19
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
#20
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
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