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Autophagy and chemotherapy resistance

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https://www.readbyqxmd.com/read/28797843/blockade-of-stearoyl-coa-desaturase-1-activity-reverts-resistance-to-cisplatin-in-lung-cancer-stem-cells
#1
Maria Elena Pisanu, Alessia Noto, Claudia De Vitis, Stefania Morrone, Giosuè Scognamiglio, Gerardo Botti, Federico Venuta, Daniele Diso, Ziga Jakopin, Fabrizio Padula, Alberto Ricci, Salvatore Mariotta, Maria Rosaria Giovagnoli, Enrico Giarnieri, Ivano Amelio, Massimiliano Agostini, Gerry Melino, Gennaro Ciliberto, Rita Mancini
Poor prognosis in lung cancer has been attributed to the presence of lung cancer stem cells (CSCs) which resist chemotherapy and cause disease recurrence. Hence, the strong need to identify mechanisms of chemoresistance and to develop new combination therapies. We have previously shown that Stearoyl-CoA-desaturase 1 (SCD1), the enzyme responsible for the conversion of saturated to monounsaturated fatty acids is upregulated in 3D lung cancer spheroids and is an upstream activator of key proliferation pathways β-catenin and YAP/TAZ...
August 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28783174/lysine-specific-demethylase-lsd1-regulates-autophagy-in-neuroblastoma-through-sesn2-dependent-pathway
#2
S Ambrosio, C D Saccà, S Amente, S Paladino, L Lania, B Majello
Autophagy is a physiological process, important for recycling of macromolecules and maintenance of cellular homeostasis. Defective autophagy is associated with tumorigenesis and has a causative role in chemotherapy resistance in leukemia and in solid cancers. Here, we report that autophagy is regulated by the lysine-specific demethylase LSD1/KDM1A, an epigenetic marker whose overexpression is a feature of malignant neoplasia with an instrumental role in cancer development. In the present study, we determine that two different LSD1 inhibitors (TCP and SP2509) as well as selective ablation of LSD1 expression promote autophagy in neuroblastoma cells...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28775276/chemotherapy-treatment-induces-an-increase-of-autophagy-in-the-luminal-breast-cancer-cell-mcf7-but-not-in-the-triple-negative-mda-mb231
#3
Christian Garbar, Corinne Mascaux, Jérôme Giustiniani, Yacine Merrouche, Armand Bensussan
Autophagy is one of the chemotherapy resistance mechanisms in breast cancer. The aim of this study was to determine the level of recruitment of the autophagy pathway in the triple-negative breast cancer (TNBC) cell line MDA-MB231 compared with that in the control luminal breast cancer cell line MCF7 before and after treatment with chemotherapy drugs. Furthermore, we investigated the relationship between autophagy and EGFR, MUC1 and IL17-receptors as activators of autophagy. Immunohistochemistry was performed in cell culture blocks using LC3b, MUC1-C, EGFR, IL17A, IL17-RA and IL17-RB antibodies...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28772211/autophagy-as-a-potential-therapeutic-target-during-epithelial-to-mesenchymal-transition-in-renal-cell-carcinoma-an-in-vitro-study
#4
Mamta Singla, Shalmoli Bhattacharyya
Cancer progression toward invasive and metastatic disease is aided by reactivation of epithelial-mesenchymal transition (EMT), involving transdifferentiation of epithelial cells into mesenchymal phenotype. This leads to increased migratory and stem cell-like features in the cells. These EMT cells are more resistant to chemotherapy and it is hypothesized that the phenomenon of autophagy induces resistance, providing a survival strategy for cells. In the present study, we induced EMT-like phenotype in renal carcinoma cells and identified corresponding higher autophagy flux in these cells...
July 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28765607/suppression-of-transposable-elements-in-leukemic-stem-cells
#5
Anthony R Colombo, Asif Zubair, Devi Thiagarajan, Sergey Nuzhdin, Timothy J Triche, Giridharan Ramsingh
Genomic transposable elements (TEs) comprise nearly half of the human genome. The expression of TEs is considered potentially hazardous, as it can lead to insertional mutagenesis and genomic instability. However, recent studies have revealed that TEs are involved in immune-mediated cell clearance. Hypomethylating agents can increase the expression of TEs in cancer cells, inducing 'viral mimicry', causing interferon signalling and cancer cell killing. To investigate the role of TEs in the pathogenesis of acute myeloid leukaemia (AML), we studied TE expression in several cell fractions of AML while tracking its development (pre-leukemic haematopoietic stem cells, leukemic stem cells [LSCs], and leukemic blasts)...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759800/mesenchymal-stem-cells-derived-from-multiple-myeloma-patients-protect-against-chemotherapy-through-autophagy-dependent-activation-of-nf-%C3%AE%C2%BAb-signaling
#6
HongLiang Yang, YingChun Zheng, YiZhuo Zhang, Zeng Cao, Yingzhe Jiang
Chemotherapy resistance has been considered as a major problem for multiple myeloma (MM) treatment and bone marrow microenvironment plays a crucial role in the MM progression and chemoresistance. Recent studies reported that bone marrow mesenchymal stem cells derived from MM patients (MM-MSCs) revealed various characteristics compared with these from healthy subjects (NM-MSCs). However, the functions and mechanisms by which MM-MSCs mediate the chemotherapy resistance of MM remain unclear. In this study, we show that MM-MSCs decreased melphalan or doxorubicin-induced cell cycle arrest and apoptosis in two MM cell lines (U266 and RPMI-8226)...
July 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28755993/breaching-barriers-in-glioblastoma-part-i-molecular-pathways-and-novel-treatment-approaches
#7
REVIEW
Ana Miranda, María Blanco-Prieto, João Sousa, Alberto Pais, Carla Vitorino
Glioblastoma multiforme (GBM) is the most common primary brain tumour, and the most aggressive in nature. The prognosis for patients with GBM remains poor, with a median survival time of only 1-2 years. The treatment failure relies on the development of resistance by tumour cells and the difficulty of ensuring that drugs effectively cross the dual blood brain barrier/blood brain tumour barrier. The advanced molecular and genetic knowledge has allowed to identify the mechanisms responsible for temozolomide resistance, which represents the standard of care in GBM, along with surgical resection and radiotherapy...
July 27, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28753429/fusobacterium-nucleatum-promotes-chemoresistance-to-colorectal-cancer-by-modulating-autophagy
#8
TaChung Yu, Fangfang Guo, Yanan Yu, Tiantian Sun, Dan Ma, Jixuan Han, Yun Qian, Ilona Kryczek, Danfeng Sun, Nisha Nagarsheth, Yingxuan Chen, Haoyan Chen, Jie Hong, Weiping Zou, Jing-Yuan Fang
Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F...
July 27, 2017: Cell
https://www.readbyqxmd.com/read/28748218/autophagy-regulated-by-mirnas-in-colorectal-cancer-progression-and-resistance
#9
Andrew Fesler, Hua Liu, Ning Wu, Fei Liu, Peixue Ling, Jingfang Ju
The catabolic process of autophagy is an essential cellular function that allows for the breakdown and recycling of cellular macromolecules. In recent years, the impact of epigenetic regulation of autophagy by non-coding microRNAs (miRNAs) has been recognized in human cancer. In colorectal cancer, Autophagy plays critical roles in cancer progression as well as resistance to chemotherapy, and recent evidence demonstrates that miRNAs are directly involved in mediating these functions. In this review, we will focus on the recent advancements in the field of miRNA regulation of autophagy in colorectal cancer...
2017: Cancer Translational Medicine
https://www.readbyqxmd.com/read/28726781/autophagy-inhibition-reduces-chemoresistance-and-tumorigenic-potential-of-human-ovarian-cancer-stem-cells
#10
Anna Pagotto, Giorgia Pilotto, Elena Laura Mazzoldi, Maria Ornella Nicoletto, Simona Frezzini, Anna Pastò, Alberto Amadori
Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as in vitro culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28707966/targeted-molecular-ablation-of-cancer-stem-cells-for-curing-gastrointestinal-cancers
#11
Yong Seok Kim, Ho Jae Lee, Jong-Min Park, Young-Min Han, Napapan Kangwan, Ji Young Oh, Dong Yoon Lee, Ki Baik Hahm
Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis...
July 14, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28701590/new-perspectives-of-cobalt-tris-bipyridine-system-anti-cancer-effect-and-its-collateral-sensitivity-towards-multidrug-resistant-mdr-cancers
#12
Betty Yuen Kwan Law, Yuan Q Qu, Simon Wing Fai Mok, Hauwei Liu, Zeng Wu, Yu Han, Flora Gordillo-Martinez, Wai-Kit Chan, Keith M Wong, Vincent Kam Wai Wong
Platinating compounds including cisplatin, carboplatin, and oxaliplatin are common chemotherapeutic agents, however, patients developed resistance to these clinical agents after initial therapeutic treatments. Therefore, different approaches have been applied to identify novel therapeutic agents, molecular mechanisms, and targets for overcoming drug resistance. In this study, we have identified a panel of cobalt complexes that were able to specifically induce collateral sensitivity in taxol-resistant and p53-deficient cancer cells...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28692436/andrographolide-enhances-cisplatin-mediated-anticancer-effects-in-lung-cancer-cells-through-blockade-of-autophagy
#13
Daolu Yuwen, Shanwei Mi, Yuzhu Ma, Wenjie Guo, Qiang Xu, Yan Shen, Yongqian Shu
Lung cancer is the most common cause of cancer-related death worldwide and the platinum-based drugs such as cisplatin have been used as the first line of the treatment. However, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance. In this study, we found that cisplatin induced autophagy that attenuated the sensitivity of both A549 and Lewis lung cancer (LLC) cells to cisplatin. In contrast, the clinical drug andrographolide (Andro) suppressed autophagy and enhanced cisplatin-mediated apoptosis in these cells...
July 7, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28678319/mir-146a-5p-level-in-serum-exosomes-predicts-therapeutic-effect-of-cisplatin-in-non-small-cell-lung-cancer
#14
D-L Yuwen, B-B Sheng, J Liu, W Wenyu, Y-Q Shu
OBJECTIVE: Lung cancer is the most common cause of death in cancer worldwide, and cisplatin plays an important role in its treatment. However, the response to chemotherapy is poorly attributable to drug resistance. Our present study aimed to investigate the relation of the exosomal miR-146a-5p level with the chemosensitivity of NSCLC to cisplatin and the molecular mechanism that miR-146a-5p mediated to effect on chemotherapy response. PATIENTS AND METHODS: The exosomes were isolated by ExoQuick kit...
June 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28677749/long-non%C3%A2-coding-rna-meg3-contributes-to-cisplatin%C3%A2-induced-apoptosis-via-inhibition-of-autophagy-in-human-glioma-cells
#15
Binbin Ma, Zebin Gao, Jiacheng Lou, Hongqiang Zhang, Zhongbo Yuan, Qiong Wu, Xinyu Li, Bo Zhang
Long non-coding RNAs (lncRNAs) function as oncogenes or tumor suppressors, and are involved in mediating tumorigenesis and resistance to chemotherapy by altering the expression of genes at various levels. Accumulating evidence suggests that the maternally expressed gene 3 (MEG3) lncRNA serves an important role in a number of cancers. However, its functional role in mediating cisplatin‑induced apoptosis of glioma cells is unknown. To investigate the role of MEG3, the mRNA levels of MEG3 under cisplatin treatment were investigated by reverse transcription‑quantitative polymerase chain reaction, and the cell viability and apoptosis were examined by MTT assay, and flow cytometry analysis and western blotting, respectively...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28670281/n-desmethyldauricine-induces-autophagic-cell-death-in-apoptosis-defective-cells-via-ca-2-mobilization
#16
Betty Y K Law, Simon W F Mok, Juan Chen, Francesco Michelangeli, Zhi-Hong Jiang, Yu Han, Yuan Q Qu, Alena C L Qiu, Su-Wei Xu, Wei-Wei Xue, Xiao-Jun Yao, Jia Y Gao, Masood-Ul-Hassan Javed, Paolo Coghi, Liang Liu, Vincent K W Wong
Resistance of cancer cells to chemotherapy remains a significant problem in oncology. Mechanisms regulating programmed cell death, including apoptosis, autophagy or necrosis, in the treatment of cancers have been extensively investigated over the last few decades. Autophagy is now emerging as an important pathway in regulating cell death or survival in cancer therapy. Recent studies demonstrated variety of natural small-molecules could induce autophagic cell death in apoptosis-resistant cancer cells, therefore, discovery of novel autophagic enhancers from natural products could be a promising strategy for treatment of chemotherapy-resistant cancer...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28656199/wnt-%C3%AE-catenin-signaling-pathway-activation-reverses-gemcitabine-resistance-by-attenuating-beclin1-mediated-autophagy-in-the-mg63-human-osteosarcoma-cell-line
#17
Hao Tao, Feng Chen, Haifei Liu, Yanling Hu, Yingzhen Wang, Haiyan Li
Anaberrant Wnt/β-catenin signaling pathway is frequently implicated in tumorigenesis. However, whether the Wnt/β‑catenin pathway plays a role in resistance to antitumor chemotherapy drugs remains unknown. In the present study, the process of autophagy was assessed following overexpression of the autophagy‑associated gene Beclin 1 in gemcitabine‑induced MG63 human osteosarcoma cells. Autophagy‑associated gene expression was measured following activation or inhibition of the Wnt/β‑catenin pathway in gemcitabine‑induced MG63 cells using reverse transcription‑quantitative polymerase chain reaction...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28656197/autophagy-plays-an-important-role-in-stemness-mediation-and-the-novel-dual-function-of-eig121-in-both-autophagy-and-stemness-regulation-of-endometrial-carcinoma-jec-cells
#18
Xiaomin Ran, Ping Zhou, Keqiang Zhang
Endometrial cancer (EC) is the third most common gynecologic malignancy in the world, and is considered a chemotherapy poor responding cancer. There are two underlying mechanisms on chemoresistance: the stemness of cancer stem cells (CSCs) and activation of pro-survival autophagy. It was found that autophagy is one of the main factors of cancer stem cell survival, multidrug resistance and maintenance of the homeostasis of cancer stem cells and normal cancer cells. However, the relationship between CSCs and autophagy of EC cells is still unknown...
June 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28650662/glucose-restriction-combined-with-autophagy-inhibition-and-chemotherapy-in-hct-116-spheroids-decreases-cell-clonogenicity-and-viability-regulated-by-tumor-suppressor-genes
#19
Monica M Schroll, Gabriel J LaBonia, Katelyn R Ludwig, Amanda B Hummon
Drug resistance is a prevalent phenomenon that decreases the efficacy of cancer treatments and contributes to cancer progression and metastasis. Weakening drug-resistant cancer cells prior to chemotherapy is a potential strategy to combat chemoresistance. One approach to damage resistant cancer cells is modulation of nutritional intake. The combination of nutrient restriction with targeted compound treatment results in pronounced molecular changes. This study provides valuable information about augmenting existing chemotherapeutic regimes with simultaneous glucose restriction and autophagy inhibition in colorectal cancer cells...
August 4, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28650490/hypoxia-induced-tumor-cell-resistance-is-overcome-by-synergistic-gapdh-sirna-and-chemotherapy-co-delivered-by-long-circulating-and-cationic-interior-liposomes
#20
Jibin Guan, Jin Sun, Feilong Sun, Bo Lou, Dong Zhang, Vida Mashayekhi, Negar Sadeghi, Gert Storm, Enrico Mastrobattista, Zhonggui He
Chemotherapeutic drug resistance of tumor cells under hypoxic conditions is caused by the inhibition of apoptosis by autophagy and drug efflux via adenosine triphosphate (ATP)-dependent transporter activation, among other factors. Here, we demonstrate that disrupting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression can reduce the autophagy and ATP levels in tumor cells. To test whether GAPDH knockdown is sufficient to overcome drug resistance, a nanocarrier (asymmetry-membrane liposome) was designed to encapsulate GAPDH-siRNA with a low dose of paclitaxel (PTX)...
July 6, 2017: Nanoscale
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