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Chloroquine and cancer

Marion Gay, Pascal Carato, Mathilde Coevoet, Nicolas Renault, Paul-Emmanuel Larchanché, Amélie Barczyk, Saïd Yous, Luc Buée, Nicolas Sergeant, Patricia Melnyk
The chloroquinoline scaffold is characteristic of anti-malarial drugs such as chloroquine (CQ) or amodiaquine (AQ). These drugs are also described for their potential effectiveness against prion disease, HCV, EBV, Ebola virus, cancer, Parkinson or Alzheimer diseases. Amyloid precursor protein (APP) metabolism is deregulated in Alzheimer's disease. Indeed, CQ modifies amyloid precursor protein (APP) metabolism by precluding the release of amyloid-beta peptides (Aβ), which accumulate in the brain of Alzheimer patients to form the so-called amyloid plaques...
March 12, 2018: Bioorganic & Medicinal Chemistry
Yan Sun, Yong-Hao Huang, Feng-Ying Huang, Wen-Li Mei, Quan Liu, Cai-Chun Wang, Ying-Ying Lin, Canhua Huang, Yue-Nan Li, Hao-Fu Dai, Guang-Hong Tan
Rationale: Cardenolides have potential as anticancer drugs. 3'-epi-12β-hydroxyfroside (HyFS) is a new cardenolide structure isolated by our research group, but its molecular mechanisms remain poorly understood. This study investigates the relationship between its antitumor activities and autophagy in lung cancer cells. Methods: Cell growth and proliferation were detected by MTT, lactate dehydrogenase (LDH) release, 5-ethynyl-20-deoxyuridine (EDU) and colony formation assays. Cell apoptosis was detected by flow cytometry...
2018: Theranostics
Xi Wu, Xue Xue, Lihui Wang, Wenjing Wang, Jian Han, Xiaoxue Sun, Haotian Zhang, Yueyang Liu, Xiaohang Che, Jingyu Yang, Chunfu Wu
Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis. Disulfiram (DSF), a drug widely used to control alcoholism, possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. Our previous studies proved that DSF/Cu exerts increased anti-tumor effects on non-small cell lung cancer (NSCLC) xenograft models, and inhibits NSCLC recurrence driven by ALDH-positive cancer stem cells...
March 13, 2018: European Journal of Pharmacology
Yangfeng Xiang, Jianqiang Zhao, Ming Zhao, Kejing Wang
Allicin has been reported to inhibit cancer cell proliferation, induce cell apoptosis and enhance the accumulation of reactive oxygen species. However, it has remained elusive whether allicin improves multidrug resistance in thyroid cancer cells through modulating autophagy. The present study demonstrated that combined use of allicin and cisplatin or carboplatin resulted in an enhanced growth inhibitory effect on SW1736 and HTh-7 cells. Furthermore, treatment with allicin significantly increased SW1736 and HTh-7 cell autophagy...
April 2018: Experimental and Therapeutic Medicine
Hiroyuki Monma, Yuichi Iida, Tamami Moritani, Tamio Okimoto, Ryosuke Tanino, Yoshitsugu Tajima, Mamoru Harada
Autophagy contributes to the treatment-resistance of many types of cancers, and chloroquine (CQ) inhibits autophagy. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) kills cancer cells but is minimally cytotoxic to normal cells. However, because the therapeutic efficacy of TRAIL is limited, it is necessary to augment TRAIL-induced anti-tumor effects. In this study, we explored the anti-tumor effects of a combination of CQ and TRAIL on two human pancreatic cancer cell lines: TRAIL-sensitive MiaPaCa-2 cells and Panc-1 cells that are less sensitive to TRAIL...
2018: PloS One
Hui-Ping Chang, Chi-Cheng Lu, Jo-Hua Chiang, Fuu-Jen Tsai, Yu-Ning Juan, Je-Wei Tsao, Hong-Yi Chiu, Jai-Sing Yang
Pterostilbene is a natural polyphenolic compound that is primarily found in fruits, such as blueberries and has a similar structure to resveratrol. Pterostilbene exhibits antioxidant, anti-inflammatory and antitumor activity but the effects of pterostilbene on drug-resistant oral cancer cells and its underlying mechanisms of action have not yet been explored. Therefore, the present study was performed to clarify the anticancer effects of pterostilbene on cisplatin-resistant human oral cancer CAR cells. The results demonstrated that CAR cells exhibited marked shrinkage, cell membrane breakage and autophagic vacuole formation following treatment with pterostilbene...
March 2, 2018: International Journal of Oncology
Laura Berliocchi, Carlotta Chiappini, Annagrazia Adornetto, Debora Gentile, Silvia Cerri, Rossella Russo, Giacinto Bagetta, Maria Tiziana Corasaniti
BACKGROUND: d-Limonene is a natural monoterpene abundant in Citrus essential oils. It is endowed with several biological activities, including inhibition of carcinogenesis and promotion of tumour regression. Recently, d-limonene has been shown to modulate autophagic markers in vitro at concentrations found in vivo, in clinical pharmacokinetic studies. Autophagy is an intracellular catabolic process serving as both an adaptive metabolic response and a quality control mechanism. Because autophagy defects have been linked to a wide range of human pathologies, including neurodegeneration and cancer, there is a need for new pharmacological tools to control deregulated autophagy...
February 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Abdullah Alshehri, Anna Grabowska, Snow Stolnik
Design of an efficient delivery system is a generally recognised bottleneck in translation of siRNA technology into clinic. Despite research efforts, cellular processes that determine efficiency of siRNA silencing achieved by different delivery formulations remain unclear. Here, we investigated the mechanism(s) of cellular internalisation of a model siRNA-loaded liposome system in a correlation to the engagement of delivered siRNA with its target and consequent silencing by adopting siRNA molecular beacon technology...
February 28, 2018: Scientific Reports
Yong-Hao Huang, Jing Lei, Guo-Hui Yi, Feng-Ying Huang, Yue-Nan Li, Cai-Chun Wang, Yan Sun, Hao-Fu Dai, Guang-Hong Tan
OBJECTIVES: Coroglaucigenin (CGN), a natural product isolated from Calotropis gigantean by our research group, has been identified as a potential anti-cancer agent. However, the molecular mechanisms involved remain poorly understood. MATERIALS AND METHODS: Cell viability and cell proliferation were detected by MTT and BrdU assays. Flow cytometry, SA-β-gal assay, western blotting and immunofluorescence were performed to determine CGN-induced apoptosis, senescence and autophagy...
February 27, 2018: Cell Proliferation
Jorge Vallecillo-Hernández, Maria Dolores Barrachina, Dolores Ortiz-Masiá, Sandra Coll, Juan Vicente Esplugues, Sara Calatayud, Carlos Hernández
NSAIDs inhibit tumorigenesis in gastrointestinal tissues and have been proposed as coadjuvant agents to chemotherapy. The ability of cancer epithelial cells to adapt to the tumour environment and to resist cytotoxic agents seems to depend on rescue mechanisms such as autophagy. In the present study we aimed to determine whether an NSAID with sensitizing properties such as indomethacin modulates autophagy in gastric cancer epithelial cells. We observed that indomethacin causes lysosomal dysfunction in AGS cells and promotes the accumulation of autophagy substrates without altering mTOR activity...
February 26, 2018: Scientific Reports
Saverio Candido, Stephen L Abrams, Linda Steelman, Kvin Lertpiriyapong, Alberto M Martelli, Lucio Cocco, Stefano Ratti, Matilde Y Follo, Ramiro M Murata, Pedro L Rosalen, Paolo Lombardi, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Pann-Gill Suh, Massimo Libra, James A McCubrey
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5-10% after diagnosis and treatment. Pancreatic cancer has been associated with type II diabetes as the frequency of recently diagnosed diabetics that develop pancreatic cancer within a 10-year period of initial diagnosis of diabetes in increased in comparison to non-diabetic patients. Metformin is a very frequently prescribed drug used to treat type II diabetes...
February 12, 2018: Advances in Biological Regulation
Paolo Coghi, Ivan A Yaremenko, Parichat Prommana, Peter S Radulov, Mikhail A Syroeshkin, Yu Jun Wu, Jia Ying Gao, Flora M Gordillo-Martinez, Simon Mok, Vincent K W Wong, Chairat Uthaipibull, Alexander O Terent'ev
Twenty six peroxides belonging to bridged 1,2,4,5-tetraoxanes, bridged 1,2,4-trioxolanes (ozonides), and tricyclic monoperoxides were evaluated for the in vitro antimalarial activity against Plasmodium falciparum (3D7) and for their cytotoxic activities against immortalized human normal fibroblast (CCD19Lu), liver (LO2) and lung (BEAS-2B) cell lines as well as human liver (HepG2) and lung (A549) cancer cell lines. Synthetic ozonides were shown to have highest cytotoxicity on HepG2 (IC50 0.19-0.59 µM) and some of these compounds selectively targeted liver cancer (SI for compounds 13a and 14a is 20 and 28 respectively), which in some cases were higher than that of paclitaxel, artemisinin, artesunic acid...
February 22, 2018: ChemMedChem
Uma Maheswari, Krishna Ghosh, Sudha Rani Sadras
Lung cancer has a relatively poor prognosis with a low survival rate and drugs that target other cell death mechanism like autophagy may help improving current therapeutic strategy. This study investigated the anti-proliferative effect of Licarin A (LCA) from Myristica fragrans in non-small cell lung cancer cell lines-A549, NCI-H23, NCI-H520 and NCI-H460. LCA inhibited proliferation of all the four cell lines in a dose and time dependent manner with minimum IC50 of 20.03 ± 3.12, 22.19 ± 1.37 µM in NCI-H23 and A549 cells respectively...
February 21, 2018: Apoptosis: An International Journal on Programmed Cell Death
Zhiping Fu, Cheng Xi, Jie Kuang, Haoran Feng, Lingxie Chen, Juyong Liang, Xiaonan Shen, Stanley Yuen, Peng Chenghong, Shen Baiyong, Jin Zhijian, Weihua Qiu
As an established anti-cancer drug, gemcitabine (GEM) is an effective systemic treatment for advanced pancreatic cancer (PC). However, little is known about the potential effectors that may modify tumour cell sensitivity towards GEM. Autophagy, as a physiological cellular mechanism, is involved in both cell survival and cell death. In this study, we found that exposure to GEM induced a significant increase in autophagy in a dose-dependent manner in PANC-1 and BxPC-3 cells. Inhibition of autophagy by chloroquine (CQ) and ATG7 siRNA increased GEM-induced cytotoxicity, and CQ was more effective than ATG7 siRNA...
February 17, 2018: Molecular Oncology
Satoshi Endo, Manami Hoshi, Toshiyuki Matsunaga, Takahiro Inoue, Kenji Ichihara, Akira Ikari
Propolis, a resinous substance produced by honeybees, possesses various biological actions including anticancer activity towards tumor cells. Recently, the ethanol extract of Brazilian green propolis has been shown to induce autophagy, which is known to be induced in treatment of cancer cells with anticancer drugs, leading to cancer cell survival and decreased sensitivity to anticancer agents. In this study, we aimed to identify autophagy-inducing components of the propolis and elucidated the reciprocal relationship between anticancer cytotoxicity and protective autophagy in prostate cancer CWR22Rv1 cells...
February 13, 2018: Biochemical and Biophysical Research Communications
Xiaoning Yan, Lei Yang, Gaili Feng, Zhuli Yu, Minjie Xiao, Weibin Cai, Yanmei Xing, Shasha Bai, Junqia Guo, Zhiyu Wang, Tao Wang, Rong Zhang
Betulin (BT), a pentacyclic lupine-type triterpenoid natural product, possesses antitumor activity in various types of cancers. However, its clinical development was discouraged due to its low biological activities and poor solubility. We prepared lup-20(29)-en-3β,28-di-yl-nitrooxy acetate (NBT), a derivative of BT, that was chemically modified at position 3 of ring A and C-28 by introducing a NO-releasing moiety. This study mainly explored the mechanism of NBT in treating breast cancer through the crosstalk between apoptosis and autophagy in mitochondria...
February 14, 2018: Cell Death & Disease
Shousheng Liu, Xiuyu Cai, Liangping Xia, Chang Jiang, Ping Chen, Xiaopai Wang, Bei Zhang, Hong Yun Zhao
Chloroquine (CQ) has been confirmed to exhibit antitumor effects on different types of cancer cell, but whether it exerts the same effect on acute promyelocytic leukemia (APL) cells remains to be confirmed. In the present study, the effects of various concentrations of CQ on the growth, apoptosis and cell cycle distribution of NB4 cells, as well as the potential mechanisms underlying these effects, were examined. The combined effect of CQ and arsenic trioxide (ATO) on the growth of NB4 cells was also determined...
February 2018: Oncology Letters
Rui Li, Xin Yi, Xiang Wei, Bo Huo, Xian Guo, Cai Cheng, Ze-Min Fang, Jing Wang, Xin Feng, Ping Zheng, Yun-Shu Su, Jackson Ferdinand Masau, Xue-Hai Zhu, Ding-Sheng Jiang
Enhancer of zeste homolog 2 (EZH2), a methyltransferase that di- and tri-methylates lysine-27 of histone H3, largely functions as a transcriptional repressor, and plays a critical role in various kinds of cancers. Here we report a novel function of EZH2 in regulating autophagic cell death (ACD) of vascular smooth muscle cells (VSMCs) that affect aortic dissection (AD). Inhibition of EZH2 activity by UNC1999 or knockdown EZH2 resulted in VSMC loss, while overexpression of EZH2 facilitated VSMC growth, and these effects of EZH2 on VSMCs were independent of proliferation and apoptosis...
February 7, 2018: Cell Death & Disease
Jesús A Romero, María E Acosta, Neira D Gamboa, Michael R Mijares, Juan B De Sanctis, Jaime E Charris
Chemically modified versions of bioactive substances, are particularly useful in overcoming barriers associated with drug formulation, drug delivery and poor pharmacokinetic properties. In this study, a series of fourteen (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate (2-15) were prepared by using a one step synthesis from 1 previously described by us as potential antimalarial and antitumor agent. Molecules were evaluated as inhibitors of β-hematin formation, where most of them showed a significant inhibition value (% > 70)...
February 2, 2018: Bioorganic & Medicinal Chemistry
Azumi Nakamura, Wataru Matsunaga, Akinobu Gotoh
AIM: Naftopidil is used to treat benign prostate hyperplasia. Moreover, previous studies have shown that naftopidil reduced viability of many types of cancer cells. Therefore, we investigated the antitumor mechanism of naftopidil in this study. MATERIALS AND METHODS: We used the HGC27 human gastric cancer cell line. It was treated with naftopidil, pan-caspase inhibitor, and chloroquine diphosphate (CQ). Cell viability and cell death were investigated by the assay and annexin V/ propidium iodide assay...
February 2018: Anticancer Research
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