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Autophagy and cancer

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https://www.readbyqxmd.com/read/27914215/lysine-specific-demethylase-1-lsd1-inhibitor-s2101-induces-autophagy-via-the-akt-mtor-pathway-in-skov3-ovarian-cancer-cells
#1
Shujun Feng, Ye Jin, Mengjiao Cui, Jianhua Zheng
BACKGROUND S2101 is one of the most potent LSD1 inhibitors, which can inhibit ovarian cancer cells viability. This study aimed to detect the mechanism behind the anticancer properties of S2101 in SKOV3 ovarian cells. MATERIAL AND METHODS Cell viability was tested by Cell Counting Kit-8 (CCK-8) assay. Cellular apoptosis and autophagy were evaluated by flow cytometric analysis using Annexin-V/PI staining methods and Green fluorescent protein (GFP)-fused-LC3 (GFP-LC3), respectively. Western blotting was performed for analyzing the Bax, Bcl-2, mTOR, p- mTOR, p62, LC3-I, LC3-II, AKT, and p-AKT protein expression...
December 3, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27913197/doxorubicin-induced-mitophagy-contributes-to-drug-resistance-in-cancer-stem-cells-from-hct8-human-colorectal-cancer-cells
#2
Chen Yan, Lan Luo, Chang-Ying Guo, Shinji Goto, Yoshishige Urata, Jiang-Hua Shao, Tao-Sheng Li
Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133(+)/CD44(+) CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs...
November 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#3
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#4
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27910983/investigation-and-intervention-of-autophagy-to-guide-cancer-treatment-with-nanogels
#5
Xudong Zhang, Xin Liang, Jianjun Gu, Danfeng Chang, Jinxie Zhang, Zhaowei Chen, Yanqi Ye, Chao Wang, Wei Tao, Xiaowei Zeng, Gan Liu, Yongjun Zhang, Lin Mei, Zhen Gu
Cancer cells use autophagy to resist poor survival environmental conditions such as low PH, poor nutrients as well as chemical therapy. Nanogels have been used as efficient chemical drug carriers for cancer treatment. However, the effect of nanogels on autophagy is still unknown. Here, we used Rab proteins as the marker of multiple trafficking vesicles in endocytosis and LC3 as the marker of autophagy to investigate the intracellular trafficking network of Rhodamine B (Rho)-labeled nanogels. The nanogels were internalized by the cells through multiple protein dependent endocytosis and micropinocytosis...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27902742/chloroquine-sensitizes-nasopharyngeal-carcinoma-cells-but-not-nasoepithelial-cells-to-irradiation-by-blocking-autophagy
#6
Anna Makowska, Michael Eble, Kirsten Prescher, Mareike Hoß, Udo Kontny
BACKGROUND: Treatment of nasopharyngeal carcinoma requires the application of high dosages of radiation, leading to severe long-term complications in the majority of patients. Sensitizing tumor cells to radiation could be a means to increase the therapeutic window of radiation. Nasopharyngeal carcinoma cells display alterations in autophagy and blockade of autophagy has been shown to sensitize them against chemotherapy. METHODS: We investigated the effect of chloroquine, a known inhibitor of autophagy, on sensitization against radiation-induced apoptosis in a panel of five nasopharyngeal carcinoma cell lines and a SV40-transformed nasoepithelial cell line...
2016: PloS One
https://www.readbyqxmd.com/read/27902471/autophagy-autophagy-associated-adaptive-immune-responses-and-its-role-in-hematologic-malignancies
#7
REVIEW
Liangshun You, Shenhe Jin, Li Zhu, Wenbin Qian
Autophagy is a tightly regulated catabolic process that leads to the degradation of cytoplasmatic components such as aggregated/misfolded proteins and organelles through the lysosomal machinery. Recent studies suggest that autophagy plays such a role in the context of the anti-tumor immune response, make it an attractive target for cancer immunotherapy. Defective autophagy in hematopoietic stem cells may contribute to the development of hematologic malignancies, including leukemia, myelodysplastic syndrome, and lymphoproliferative disorder...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901496/cancer-initiating-cells-are-enriched-in-the-ca9-positive-fraction-of-primary-cervix-cancer-xenografts
#8
Delphine Tamara Marie-Egyptienne, Naz Chaudary, Tuula Kalliomäki, David William Hedley, Richard Peter Hill
Numerous studies have suggested that Cancer Initiating Cells (CIC) can be identified/enriched in cell populations obtained from solid tumors based on the expression of cell surface marker proteins. We used early passage primary cervix cancer xenografts to sort cells based on the expression of the intrinsic hypoxia marker Carbonic Anhydrase 9 (CA9) and tested their cancer initiation potential by limiting dilution assay. We demonstrated that CICs are significantly enriched in the CA9+ fraction in 5/6 models studied...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900002/therapeutic-targeting-of-liver-cancer-with-a-recombinant-dna-vaccine-containing-the-hemagglutinin-neuraminidase-gene-of-newcastle-disease-virus-via-apoptotic-dependent-pathways
#9
Li-Gang Chen, Yuan-Sheng Liu, Tang-Hui Zheng, Xu Chen, Ping Li, Chuan-Xing Xiao, Jian-Lin Ren
A total of ~38.6 million mortalities occur due to liver cancer annually, worldwide. Although a variety of therapeutic methods are available, the efficacy of treatment at present is extremely limited due to an increased risk of malignancy and inherently poor prognosis of liver cancer. Gene therapy is considered a promising option, and has shown notable potential for the comprehensive therapy of liver cancer, in keeping with advances that have been made in the development of cancer molecular biology. The present study aimed to investigate the synergistic effects of the abilities of the hemagglutinin neuraminidase protein of Newcastle disease virus (NDV), the pro-apoptotic factor apoptin from chicken anaemia virus, and the interferon-γ inducer interleukin-18 (IL-18) in antagonizing liver cancer...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899303/gambogic-acid-counteracts-mutant-p53-stability-by-inducing-autophagy
#10
Giorgia Foggetti, Laura Ottaggio, Debora Russo, Paola Monti, Paolo Degan, Gilberto Fronza, Paola Menichini
Mutant p53 (mutp53) proteins are frequently present at higher levels than the wild-type (wt) protein in tumors, and some of them can acquire oncogenic properties. Consistently, knockdown of mutp53 protein in human cancer cell lines leads to reduced cell proliferation and invasion as well as to an increased sensitivity to some anticancer drugs. Therefore, the exploitation of cellular pathways and/or molecules that promote mutp53 degradation may have a therapeutic interest. Recently, autophagy is emerging as an important pathway involved in the stability of mutp53...
November 26, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27899257/juglanin-induces-apoptosis-and-autophagy-in-human-breast-cancer-progression-via-ros-jnk-promotion
#11
Zhu-Lei Sun, Jin-Long Dong, Jiang Wu
Breast cancer is one of the most common primary malignant tumors of among women, the long-term survival of which has stagnated in the past decades. Juglanin as a natural production mainly extracted from green walnut husks of Juglans mandshurica has been defined as the functional composition among a series of compounds. It showed powerful protective effect in various diseases by inhibiting inflammation and tumor cells growth. However, the effect of juglanin on human breast cancer and the underlying mechanisms remains to be elucidated...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27899249/ginsenoside-20-s-rg3-induced-autophagy-to-inhibit-migration-and-invasion-of-ovarian-cancer
#12
Xia Zheng, Wei Chen, Huilian Hou, Jie Li, Huijin Li, Xiaomin Sun, Le Zhao, Xu Li
BACKGROUND: Autophagy maintains cellular homeostasis through engulfing cytoplasmic proteins and organelles, and plays an important role in cancer initiation and progression. Ginsenoside 20(S)-Rg3, an active ingredient of Panax ginseng, exerts anti-cancer functions in various cancers. However, its molecular mechanisms, including its effect on autophagy, are not fully elucidated in tumor models. METHODS: Ovarian cancer cell line SKOV3 was treated by various concentrations of 20(S)-Rg3...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27897991/the-double-role-of-p53-in-cancer-and-autoimmunity-and-its-potential-as-therapeutic-target
#13
REVIEW
Alessandra Fierabracci, Marsha Pellegrino
p53 is a sequence-specific short-lived transcription factor expressed at low concentrations in various tissues while it is upregulated in damaged, tumoral or inflamed tissue. In normally proliferating cells, p53 protein levels and function are tightly controlled by main regulators, i.e., MDM2 (mouse double minute 2) and MDM4 proteins. p53 plays an important role due to its ability to mediate tumor suppression. In addition to its importance as a tumor suppressor, p53 coordinates diverse cellular responses to stress and damage and plays an emerging role in various physiological processes, including fertility, cell metabolism, mitochondrial respiration, autophagy, cell adhesion, stem cell maintenance and development...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27897164/hmgb1-mediated-autophagy-decreases-sensitivity-to-oxymatrine-in-sw982-human-synovial-sarcoma-cells
#14
Yongsong Cai, Peng Xu, Le Yang, Ke Xu, Jialin Zhu, Xiaoqing Wu, Congshan Jiang, Qiling Yuan, Bo Wang, Yuanbo Li, Yusheng Qiu
Oxymatrine (OMT) is a type of alkaloid extracted from a traditional Chinese medicinal herb, Sophora flavescens. Although the antitumor activities of OMT have been observed in various cancers, there are no reports regarding the effects of OMT on human synovial sarcoma. In the present study, we analyzed the antitumor activities of OMT in SW982 human synovial sarcoma cells and determine whether high mobility group box protein 1 (HMGB1)-mediated autophagy was associated with its therapeutic effects. We found that OMT exhibited antitumor activity in SW982 cells and facilitated increases in autophagy...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896219/enhanced-therapeutic-efficacy-in-cancer-patients-by-short-term-fasting-the-autophagy-connection
#15
REVIEW
Gustav van Niekerk, Suzèl M Hattingh, Anna-Mart Engelbrecht
Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy toward cell maintenance and repair processes, rather than growth and proliferation...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27896217/adapt-recycle-and-move-on-proteostasis-and-trafficking-mechanisms-in-melanoma
#16
REVIEW
Seyma Demirsoy, Shaun Martin, Hannelore Maes, Patrizia Agostinis
Melanoma has emerged as a paradigm of a highly aggressive and plastic cancer, capable to co-opt the tumor stroma in order to adapt to the hostile microenvironment, suppress immunosurveillance mechanisms, and disseminate. In particular, oncogene- and aneuploidy-driven dysregulations of proteostasis in melanoma cells impose a rewiring of central proteostatic processes, such as the heat shock and unfolded protein responses, autophagy, and the endo-lysosomal system, to avoid proteotoxicity. Research over the past decade has indicated that alterations in key nodes of these proteostasis pathways act in conjunction with crucial oncogenic drivers to increase intrinsic adaptations of melanoma cells against proteotoxic stress, modulate the high metabolic demand of these cancer cells and the interface with other stromal cells, through the heightened release of soluble factors or exosomes...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27896021/lithocholic-acid-induces-endoplasmic-reticulum-stress-autophagy-and-mitochondrial-dysfunction-in-human-prostate-cancer-cells
#17
Ahmed A Gafar, Hossam M Draz, Alexander A Goldberg, Mohamed A Bashandy, Sayed Bakry, Mahmoud A Khalifa, Walid AbuShair, Vladimir I Titorenko, J Thomas Sanderson
Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells...
2016: PeerJ
https://www.readbyqxmd.com/read/27895802/vitamin-c-induces-apoptosis-in-ags-cells-via-production-of-ros-of-mitochondria
#18
Jae Young Lim, Donghyun Kim, Bok Ran Kim, Jin Su Jun, Jung Sook Yeom, Ji Sook Park, Ji-Hyun Seo, Chan Hoo Park, Hyang Ok Woo, Hee-Shang Youn, Seung-Chul Baik, Woo-Kon Lee, Myung-Je Cho, Kwang-Ho Rhee
It has been demonstrated that vitamin C exhibits anti-cancer activity in various tumor cell lines; however, its specific mechanism of action remains unknown. Although the diagnosis and therapy of cancer patients have markedly improved in recent years, safer and more cost-effective treatments are still required. Therefore, the present study examined the effect of vitamin C on the induction of cell death in gastric cancer and its underlying mechanism of action. It was observed that the cytotoxicity of vitamin C on the human gastric cancer cell line AGS is dependent on the apoptotic pathway, including caspase cascades, but not on the necroptotic pathway...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895792/microrna-199a-5p-inhibits-cisplatin-induced-drug-resistance-via-inhibition-of-autophagy-in-osteosarcoma-cells
#19
Yusheng Li, Wei Jiang, Yuling Hu, Zixun Da, Chao Zeng, Min Tu, Zhenhan Deng, Wenfeng Xiao
Osteosarcoma (OS) is the most common cancer of the bone. Chemotherapy is commonly used for the clinical treatment of OS. However, chemoresistance to cisplatin [also known as diamminedichloridoplatinum (II) (DDP)] is a major obstacle for OS therapy, the underlying mechanism of which is not fully understood. The present study aimed to investigate the role of microRNA (miR)-199a-5p in the regulation of chemoresistance to DDP in OS cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that the expression level of miR-199a-5p was significantly reduced in human OS MG63 cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895729/celastrus-orbiculatus-extract-triggers-apoptosis-and-autophagy-via-pi3k-akt-mtor-inhibition-in-human-colorectal-cancer-cells
#20
Lin Yang, Yanqing Liu, Mei Wang, Yayun Qian, Xiaojun Dai, Yaodong Zhu, Jue Chen, Shiyu Guo, Tadashi Hisamitsu
Celastrus orbiculatus is used as a folk medicine in China for the treatment of numerous diseases. The ethyl acetate extract of Celastrus orbiculatus (COE) also displays a wide range of anti-cancer activities in the laboratory. However, the effectiveness of COE-induced autophagy and its mechanism of action in colorectal cancer cells have not been investigated thus far. The present study analyzed the effect of COE on HT-29 cell viability, apoptosis and autophagy using MTT assay, flow cytometry, transmission electron microscopy and western blotting...
November 2016: Oncology Letters
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