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Chloroquine and cancer

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https://www.readbyqxmd.com/read/28441548/ferrocenyl-and-organic-novobiocin-derivatives-synthesis-and-their-in-vitro-biological-activity
#1
Mziyanda Mbaba, Amanda N Mabhula, Natasha Boel, Adrienne L Edkins, Michelle Isaacs, Heinrich C Hoppe, Setshaba D Khanye
A focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. These compounds were screened for biological activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted in compounds 6a-d/6f showing enhanced activity compared to organic analogues 5a-b and 5e-f...
April 13, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28433067/chloroquine-and-hydroxychloroquine-inhibit-bladder-cancer-cell-growth-by-targeting-basal-autophagy-and-enhancing-apoptosis
#2
Yi-Chia Lin, Ji-Fan Lin, Sheng-I Wen, Shan-Che Yang, Te-Fu Tsai, Hung-En Chen, Kuang-Yu Chou, Thomas I-Sheng Hwang
Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7)...
May 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28431282/the-role-of-pharmacologic-modulation-of-autophagy-on-anal-cancer-development-in-an-hpv-mouse-model-of-carcinogenesis
#3
Brooks L Rademacher, Kristina A Matkowskyj, Louise M Meske, Alexis Romero, Hana Sleiman, Evie H Carchman
Autophagy is an intracellular, catabolic process that maintains cellular health. We examined the response of pharmacologic modulation of autophagy in an HPV mouse model of anal carcinogenesis. K14E6/E7 mice were treated with the topical carcinogen DMBA weekly and assessed for tumors over 20 weeks. Concurrently, they were given either chloroquine or BEZ235, to inhibit or induce autophagy, respectively. Time to tumor onset was examined. Immunofluorescence (IF) was performed for LC3β and p62 to examine autophagy...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28424408/synthetic-lethality-of-glutaminolysis-inhibition-autophagy-inactivation-and-asparagine-depletion-in-colon-cancer
#4
Jiaqiu Li, Ping Song, Liyuan Zhu, Neelum Aziz, Qiyin Zhou, Yulong Zhang, Wenxia Xu, Lifeng Feng, Dingwei Chen, Xian Wang, Hongchuan Jin
Cancer cells reprogram metabolism to coordinate their rapid growth. They addict on glutamine metabolism for adenosine triphosphate generation and macromolecule biosynthesis. In this study, we report that glutamine deprivation retarded cell growth and induced prosurvival autophagy. Autophagy inhibition by chloroquine significantly enhanced glutamine starvation induced growth inhibition and apoptosis activation. Asparagine deprivation by L-asparaginase exacerbated growth inhibition induced by glutamine starvation and autophagy blockage...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414310/autophagy-supports-generation-of-cells-with-high-cd44-expression-via-modulation-of-oxidative-stress-and-parkin-mediated-mitochondrial-clearance
#5
K A Whelan, P M Chandramouleeswaran, K Tanaka, M Natsuizaka, M Guha, S Srinivasan, D S Darling, Y Kita, S Natsugoe, J D Winkler, A J Klein-Szanto, R K Amaravadi, N G Avadhani, A K Rustgi, H Nakagawa
High CD44 expression is associated with enhanced malignant potential in esophageal squamous cell carcinoma (ESCC), among the deadliest of all human carcinomas. Although alterations in autophagy and CD44 expression are associated with poor patient outcomes in various cancer types, the relationship between autophagy and cells with high CD44 expression remains incompletely understood. In transformed oesophageal keratinocytes, CD44(Low)-CD24(High) (CD44L) cells give rise to CD44(High)-CD24(-/Low) (CD44H) cells via epithelial-mesenchymal transition (EMT) in response to transforming growth factor (TGF)-β...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28378765/a-lignan-induces-lysosomal-dependent-degradation-of-foxm1-protein-to-suppress-%C3%AE-catenin-nuclear-translocation
#6
Guang-Zhi Dong, Ji Hye Jeong, Yu-Ih Lee, Yeong Eun Han, Jung Sook Shin, Yoon-Jung Kim, Raok Jeon, Young Hwa Kim, Tae Jun Park, Keun Il Kim, Jae-Ha Ryu
Colon cancer is one of the most common cancers. In this study, we isolated a lignan [(-)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica (Betulaceae) and investigated its biological activity and mechanism of action on colon cancer. DFS reduced the viability of colon cancer cells and induced cell cycle arrest. DFS also suppressed β-catenin nuclear translocation and β-catenin target gene expression through a reduction in FoxM1 protein. To assess the mechanism of the action of DFS, we investigated the effect of DFS on endogenous and exogenous FoxM1 protein degradation in colon cancer cells...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28367822/-autophagy-contributes-to-the-initiation-of-pancreatic-cancer
#7
Juan L Iovanna
The pancreatic adenocarcinoma initiation results from the interaction of genetic events combined with multiple other factors. Among the genetic alterations that contribute to the pathogenesis of this disease, the mutation of the KRAS oncogene is required but not sufficient to trigger this cancer. Pancreatitis, an inflammatory disease, facilitates and accelerates the transformation of pancreatic cells when the KRAS oncogene is mutated. Of note, the repertoire of molecular mediators of pancreatitis which are responsible of the promotion of KRAS-mediated transformation is not completely defined...
March 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28359249/autophagy-inhibition-in-childhood-nephroblastoma-and-the-therapeutic-significance
#8
Lin-Jie Li, Yi-Long Wang, Lin-Qing Yuan, Wei-Zhong Gu, Kun Zhu, Min Yang, Duo Zhou, Yao Lv, Min-Ju Li, Zheng-Yan Zhao, Jin-Hu Wang, Xi Chen
Autophagy is a physiological pathway characterized by lysosome-dependent self-digestion to recycle damaged or superfluous cellular content. Deregulation of autophagy hampers the maintenance of cellular homeostasis and contributes to tumorigenesis. However, during anticancer therapy, autophagy activation contributes to development of resistance. Thus autophagy has been recognized as an important pathway and a therapeutic target in cancer. Nephroblastoma (Wilm's tumor) is a common childhood malignancy, the prognosis of the metastatic and relapsed cases remains poor...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28358368/a-novel-and-promising-therapeutic-approach-for-nsclc-recombinant-human-arginase-alone-or-combined-with-autophagy-inhibitor
#9
Weitao Shen, Xuyao Zhang, Xiang Fu, Jiajun Fan, Jingyun Luan, Zhonglian Cao, Ping Yang, Zhongyuan Xu, Dianwen Ju
Recombinant human arginase (rhArg), an enzyme capable of depleting arginine, has been shown to be an effective therapeutic approach for various cancers. Non-small-cell lung cancer (NSCLC), a histological subtype of pulmonary carcinoma, has a high rate of morbidity and mortality in the world. Thus, the need for novel and more effective treatment is urgent. In this study, it is the first time to report that rhArg could induce significant cytotoxicity and caspase-dependent apoptosis in NSCLC cells. Subsequently, our research revealed that rhArg dramatically stimulated autophagic response in NSCLC cells, which was proved by the formation and accumulation of autophagosomes and the conversion of microtubule-associated protein light chain 3 (LC3) from LC3-I to LC3-II...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28356017/antitumor-activity-of-copper-i-nicotinate-complex-and-autophagy-modulation-in-hcc1806-breast-cancer-cells
#10
Mohamed A Abdel-Mohsen, Eman S El-Shafey, Camelia A Abdel Malak, Morsy M Abou-Yossef
BACKGROUND: TNBC is a heterogeneous aggressive disease, therefore, its treatment is challenging. Increased attention has been paid to metal complexes as anticancer drugs. However, new insights towards autophagy have been recognized due to its role in tumor cell death or survival. OBJECTIVE: To clarify the antitumor activity of copper (I) nicotinate complex (CNC) as new therapeutic agent and understand the role of autophagy modulation as a prospective target for the advancement of efficient therapeutic agent for TNBC treatment...
March 27, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28352997/deprivation-of-asparagine-triggers-cytoprotective-autophagy-in-laryngeal-squamous-cell-carcinoma
#11
Yunxiang Ji, Li Li, Qilei Tao, Xuyao Zhang, Jingyun Luan, Shuwei Zhao, Huanhai Liu, Dianwen Ju
Laryngeal squamous cell carcinoma (LSCC), one of the most common malignancies in the head and neck, has poor prognosis and high mortality. The need of novel and effective treatment for LSCC is urgent. Asparaginase, an enzyme-depriving asparagine, has been employed for the treatment of various cancers. In this study, we reported for the first time that asparaginase could induce remarkable cytotoxicity and caspase-dependent apoptosis in human LSCC Tu212 and Tu686 cells. Meanwhile, autophagy was triggered by asparaginase in LSCC cells, which was confirmed by accumulation of autophagosomes and the conversion of light chain 3-I (LC3-I) to LC3-II...
March 28, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28348518/combination-of-endothelial-monocyte-activating-polypeptide-ii-with-temozolomide-suppress-malignant-biological-behaviors-of-human-glioblastoma-stem-cells-via-mir-590-3p-macc1-inhibiting-pi3k-akt-mtor-signal-pathway
#12
Wei Zhou, Libo Liu, Yixue Xue, Jian Zheng, Xiaobai Liu, Jun Ma, Zhen Li, Yunhui Liu
This study aims to investigate the effect of Endothelial-Monocyte-Activating Polypeptide-II (EMAP-II) combined with temozolomide (TMZ) upon glioblastoma stem cells (GSCs) and its possible molecular mechanisms. In this study, combination of EMAP-II with TMZ inhibited cell viability, migration and invasion in GSCs, and autophagy inhibitor 3-methyl adenine (3-MA) and chloroquine (CQ) partly reverse the anti-proliferative effect of the combination treatment. Autophagic vacuoles were formed in GSCs after the combination therapy, accompanied with the up-regulation of LC3-II and Beclin-1 as well as the down-regulation of p62/SQSTM1...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28342290/verapamil-treatment-induces-cytoprotective-autophagy-by-modulating-cellular-metabolism
#13
Elżbieta Kania, Beata Pająk, Jim O'Prey, Pablo Sierra Gonzalez, Anna Litwiniuk, Kaja Urbańska, Kevin M Ryan, Arkadiusz Orzechowski
Verapamil, an L-type calcium channel blocker, has been used successfully to treat cardiovascular diseases. Interestingly, we have recently shown that treatment of cancer cells with verapamil causes an effect on autophagy. As autophagy is known to modulate chemotherapy responses, this prompted us to explore the impact of verapamil on autophagy and cell viability in greater detail. We report here that verapamil causes an induction of autophagic flux in a number or tumor cells and immortalized normal cells. Moreover, we found that inhibition of autophagy in COLO 205 cells, via treatment with the chloroquine (CQ) or by CRISPR/Cas9-mediated disruption of the autophagy genes Atg7 and Atg5, causes an upregulation of apoptotic markers in response to verapamil...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28337019/apigenin-induced-lysosomal-degradation-of-%C3%AE-catenin-in-wnt-%C3%AE-catenin-signaling
#14
Chung-Ming Lin, Hsin-Han Chen, Chun-An Lin, Hui-Chung Wu, Jim Jinn-Chyuan Sheu, Hui-Jye Chen
The bioflavonoid apigenin has been shown to possess cancer-preventive and anti-cancer activities. In a drug screening, we found that apigenin can inhibit Wnt/β-catenin signaling, a pathway that participates in pivotal biological functions, which dis-regulation results in various human diseases including cancers. However, the underlying mechanism of apigenin in this pathway and its link to anti-cancer activities remain largely unknown. Here we showed that apigenin reduced the amount of total, cytoplasmic, and nuclear β-catenin, leading to the suppression in the β-catenin/TCF-mediated transcriptional activity, the expression of Wnt target genes, and cell proliferation of Wnt-stimulated P19 cells and Wnt-driven colorectal cancer cells...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288416/induction-of-reactive-oxygen-species-stimulated-distinctive-autophagy-by-chelerythrine-in-non-small-cell-lung-cancer-cells
#15
Zheng-Hai Tang, Wen-Xiang Cao, Zhao-Yu Wang, Jia-Hong Lu, Bo Liu, Xiuping Chen, Jin-Jian Lu
Chelerythrine (CHE), a natural benzo[c]phenanthridine alkaloid, shows anti-cancer effect through a number of mechanisms. Herein, the effect and mechanism of the CHE-induced autophagy, a type II programmed cell death, in non-small cell lung cancer (NSCLC) cells were studied for the first time. CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a concentration-dependent manner in NSCLC A549 and NCI-H1299 cells. In addition, CHE triggered the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II)...
March 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/28243469/nos1-s-nitrosylates-pten-and-inhibits-autophagy-in-nasopharyngeal-carcinoma-cells
#16
Lingqun Zhu, Linlin Li, Qianbing Zhang, Xiao Yang, Zhiwei Zou, Bingtao Hao, Francesco M Marincola, Zhengjun Liu, Zhuo Zhong, Meng Wang, Xiaoxuan Li, Qianli Wang, Keyi Li, Wenwen Gao, Kaitai Yao, Qiuzhen Liu
Autophagy is a cellular survival mechanism that involves the catabolic degradation of damaged proteins and organelles during periods of metabolic stress, and when overly stimulated, commonly contributes to cell death. Nitric oxide (NO), a potent cellular messenger, participates in a complex mechanism which assists in controlling autophagy. However, the mechanism by which endogenous NO formed by distinct isoforms of nitric oxide synthase (NOS) helps to regulate autophagy in cancer cells remains unclear. Here we report that NOS1 reduces excessive levels of autophagy and promotes the survival of nasopharyngeal carcinoma cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28240051/microrna-185-induces-potent-autophagy-via-akt-signaling-in-hepatocellular-carcinoma
#17
Li Zhou, Shunai Liu, Ming Han, Shenghu Feng, Jinqiu Liang, Zhongshu Li, Yaru Li, Hongping Lu, Ting Liu, Yanhua Ma, Jun Cheng
Studies have demonstrated that microRNA 185 may be a promising therapeutic target in liver cancer. However, its role in hepatocellular carcinoma is largely unknown. In this study, the proliferation of human HepG2 cells was inhibited by transfection of microRNA 185 mimics. Cell-cycle analysis revealed arrest at the G0/G1 phase. Transfection of HepG2 cells with microRNA 185 mimics significantly induced apoptosis. These data confirmed microRNA 185 as a potent cancer suppressor. We demonstrated that microRNA 185 was a compelling inducer of autophagy, for the first time...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28237877/osimertinib-induces-autophagy-and-apoptosis-via-reactive-oxygen-species-generation-in-non-small-cell-lung-cancer-cells
#18
Zheng-Hai Tang, Wen-Xiang Cao, Min-Xia Su, Xiuping Chen, Jin-Jian Lu
Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR T790M mutation. Herein, we indicated for the first time that OSI increased the accumulations of cytoplasmic vacuoles, the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II), and the formation of GFP-LC3 puncta in various cancer cells...
April 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28219700/inhibition-of-ros-production-autophagy-or-apoptosis-signaling-reversed-the-anticancer-properties-of-antrodia-salmonea-in-triple-negative-breast-cancer-mda-mb-231-cells
#19
Chia-Ting Chang, Mallikarjuna Korivi, Hui-Chi Huang, Varadharajan Thiyagarajan, Kai-Yuan Lin, Pei-Jane Huang, Jer-Yuh Liu, You-Cheng Hseu, Hsin-Ling Yang
We investigated the in vitro and in vivo anticancer properties of Antrodia salmonea (AS), a well-known edible/medicinal mushroom in Taiwan, on human triple-negative breast cancer (MDA-MB-231) cells and xenografted nude mice; and revealed the underlying molecular mechanisms involved in autophagic- and apoptotic-cell death. Treatment of MDA-MB-231 cells with fermented culture broth of AS (0-200 μg/mL) inhibited cell viability/growth. AS-induced autophagy was evidenced via increased LC3-II accumulation, GFP-LC3 puncta and AVOs formation in MDA-MB-231 cells...
February 20, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28208617/inhibition-of-autophagy-by-deguelin-sensitizes-pancreatic-cancer-cells-to-doxorubicin
#20
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
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