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Autophagy and chemoresistance

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https://www.readbyqxmd.com/read/28445132/targeting-autophagic-cancer-stem-cells-to-reverse-chemoresistance-in-human-triple-negative-breast-cancer
#1
Guilhem Bousquet, Morad El Bouchtaoui, Tan Sophie, Christophe Leboeuf, Cédric de Bazelaire, Philippe Ratajczak, Sylvie Giacchetti, Anne de Roquancourt, Philippe Bertheau, Laurence Verneuil, Jean-Paul Feugeas, Marc Espié, Anne Janin
There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents.Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage.We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC)...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431397/sensitization-of-tamoxifen-resistant-breast-cancer-cells-by-z-ligustilide-through-inhibiting-autophagy-and-accumulating-dna-damages
#2
Hongyi Qi, Zhuyun Jiang, Chengqiang Wang, Yi Yang, Li Li, Hui He, Zanyang Yu
Autophagy plays a pro-survival role in the tamoxifen-resistant breast cancer cells. Herein we found that autophagy was concomitantly induced in tamoxifen-resistant MCF-7 (MCF-7TR5) cells through the dissociation of Bcl-2 from Beclin 1 and subsequent enhancement of interaction among the ATG14-Beclin1-PI3KC3 complex. Moreover, higher level of DNA damage was observed in MCF-7TR5 cells with the decreased BRCA1 and RAD51 level and the increased Ku80 level. Interestingly, Nur77 was selectively degraded by autophagy, which causes the release of Ku80 from the Nur77-Ku80 complex, resulting in the increase of the DNA binding of Ku80 and DNA-PKcs...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415557/long-non-coding-rna-cta-sensitizes-osteosarcoma-cells-to-doxorubicin-through-inhibition-of-autophagy
#3
Zhengguang Wang, Zhendong Liu, Song Wu
Recently, several long non-coding RNAs (lncRNAs) have been implicated in osteosarcoma (OS). However, the regulatory roles of lncRNAs in chemotherapy resistance of OS still remain unclear. This study aimed to screen a novel lncRNA that contributes to chemotherapeutic resistance of OS, and to explore the underlying mechanisms. Our data showed that lncRNA CTA was markedly downregulated in OS tissues compared to their matched non-tumor tissues, and low expression of lncRNA CTA was significantly associated with the advanced clinical stage and tumor size...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408137/4-acetylantroquinonol-b-suppresses-autophagic-flux-and-improves-cisplatin-sensitivity-in-highly-aggressive-epithelial-cancer-through-the-pi3k-akt-mtor-p70s6k-signaling-pathway
#4
Mingche Liu, Oluwaseun Adebayo Bamodu, Wen-Chien Huang, Muhammad Ary Zucha, Yen-Kuang Lin, Alexander T H Wu, Chun-Chih Huang, Wei-Hwa Lee, Chiou-Chung Yuan, M Hsiao, Li Deng, Yew-Min Tzeng, Chi-Tai Yeh
Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg)...
April 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28404910/thalidezine-a-novel-ampk-activator-eliminates-apoptosis-resistant-cancer-cells-through-energy-mediated-autophagic-cell-death
#5
Betty Yuen Kwan Law, Flora Gordillo-Martínez, Yuan Qing Qu, Ni Zhang, Su Wei Xu, Paolo Saul Coghi, Simon Wing Fai Mok, Jianru Guo, Wei Zhang, Elaine Lai Han Leung, Xing Xing Fan, An Guo Wu, Wai Kit Chan, Xiao Jun Yao, Jing Rong Wang, Liang Liu, Vincent Kam Wai Wong
Cancers illustrating resistance towards apoptosis is one of the main factors causing clinical failure of conventional chemotherapy. Innovative therapeutic methods which can overcome the non-apoptotic phenotype are needed. The AMP-activated protein kinase (AMPK) is the central regulator of cellular energy homeostasis, metabolism, and autophagy. Our previous study showed that the identified natural AMPK activator is able to overcome apoptosis-resistant cancer via autophagic cell death. Therefore, AMPK is an ideal pharmaceutical target for chemoresistant cancers...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28382796/inhibition-of-autophagy-protein-lc3a-as-a-therapeutic-target-in-ovarian-clear-cell-carcinomas
#6
Morikazu Miyamoto, Masashi Takano, Tadashi Aoyama, Hiroaki Soyama, Tomoyuki Yoshikawa, Hitoshi Tsuda, Kenichi Furuya
OBJECTIVE: Ovarian clear cell carcinoma (CCC) is one of histological subtypes showing poor prognosis due to chemoresistance. The association of autophagy-related proteins and clinical implementation in CCC has not been determined. METHODS: The present study investigated whether expression of autophagy-related protein, light chain 3A (LC3A), was related with prognoses in the patients with CCC using immuno-histochemical stainings, and whether inhibition of autophagy modified the sensitivity to cisplatin in CCC cells in vitro...
May 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/28375488/a-combination-of-pterostilbene-with-autophagy-inhibitors-exerts-efficient-apoptotic-characteristics-in-both-chemosensitive-and-chemoresistant-lung-cancer-cells
#7
Ming-Ju Hsieh, Chiao-Wen Lin, Shun-Fa Yang, Gwo-Tarng Sheu, Ya-Yen Yu, Mu-Kuan Chen, Hui-Ling Chiou
No abstract text is available yet for this article.
April 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28373437/salinomycin-induces-reactive-oxygen-species-and-apoptosis-in-aggressive-breast-cancer-cells-as-mediated-with-regulation-of-autophagy
#8
Kwang-Youn Kim, Kwang Il Park, Sang-Hun Kim, Sun-Nyoung Yu, Deokjae Lee, Young Woo Kim, Kyung Tae Noh, Jin Yeul Ma, Young-Kyo Seo, Soon-Cheol Ahn
BACKGROUND/AIM: Chemotherapy is a critical option for cancer treatment. However, consistent exposure to chemotherapeutic drugs promotes chemoresistance in cancer cells through diverse mechanisms. Accordingly, we investigated whether salinomycin, a monocarboxylic ionophore, could induce apoptosis in aggressive breast cancer cells or not, as well as its underlying mechanism. MATERIALS AND METHODS: Using salinomycin on two breast cancer cell lines, MCF-7 cells and MDA-MB-231 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, caspase-3/9 activity, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assayed...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28356957/autophagy-impacts-on-oxaliplatin-induced-hepatocarcinoma-apoptosis-via-the-il-17-il-17r-jak2-stat3-signaling-pathway
#9
Jinghua Wu, Jiapei Guo, Qing Cao, Yi Wang, Junmao Chen, Zhigang Wang, Zhiyong Yuan
The interleukin (IL)-17/IL-17 receptor (IL-17R) complex has been shown to be important for the regulation of inflammation; however, its role in the regulation of tumor processes has recently emerged as a research focus. The present study demonstrated that oxaliplatin was able to increase the levels of IL-17/IL-17R in hepatocellular carcinoma (HCC) patients and cells lines, and that it had important roles in reducing the susceptibility of the cells to oxaliplatin-induced apoptosis. Furthermore, the expression of autophagy-related proteins was induced by IL-17/IL-17R and autophagy was shown to induce resistance to oxaliplatin in HCC...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28351381/the-role-of-stromal-cancer-associated-fibroblasts-in-pancreatic-cancer
#10
REVIEW
Dagny von Ahrens, Tushar D Bhagat, Deepak Nagrath, Anirban Maitra, Amit Verma
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer generally refractory to conventional treatments. Cancer-associated fibroblasts (CAFs) are cellular components of the desmoplastic stroma characteristic to the tumor that contributes to this treatment resistance. Various markers for CAFs have been explored including palladin and CD146 that have prognostic and functional roles in the pathobiology of PDAC. Mechanisms of CAF-tumor cell interaction have been described including exosomal transfer and paracrine signaling mediated by cytokines such as GM-CSF and IL-6...
March 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28349991/antiproliferative-effects-of-ruthenium-based-nucleolipidic-nanoaggregates-in-human-models-of-breast-cancer-in-vitro-insights-into-their-mode-of-action
#11
Carlo Irace, Gabriella Misso, Antonella Capuozzo, Marialuisa Piccolo, Claudia Riccardi, Alessandra Luchini, Michele Caraglia, Luigi Paduano, Daniela Montesarchio, Rita Santamaria
Looking for new metal-based anticancer treatments, in recent years many ruthenium complexes have been proposed as effective and safe potential drugs. In this context we have recently developed a novel approach for the in vivo delivery of Ru(III) complexes, preparing stable ruthenium-based nucleolipidic nanoaggregates endowed with significant antiproliferative activity. Herein we describe the cellular response to our ruthenium-containing formulations in selected models of human breast cancer. By in vitro bioscreens in the context of preclinical studies, we have focused on their ability to inhibit breast cancer cell proliferation by the activation of the intrinsic apoptotic pathway, possibly via mitochondrial perturbations involving Bcl-2 family members and predisposing to programmed cell death...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28347245/cancer-stem-cells-the-potential-role-of-autophagy-proteolysis-and-cathepsins-in-glioblastoma-stem-cells
#12
REVIEW
Joachim Bischof, Mike-Andrew Westhoff, Johanna Elisabeth Wagner, Marc-Eric Halatsch, Stephanie Trentmann, Uwe Knippschild, Christian Rainer Wirtz, Timo Burster
One major obstacle in cancer therapy is chemoresistance leading to tumor recurrence and metastasis. Cancer stem cells, in particular glioblastoma stem cells, are highly resistant to chemotherapy, radiation, and immune recognition. In case of immune recognition, several survival mechanisms including, regulation of autophagy, proteases, and cell surface major histocompatibility complex class I molecules, are found in glioblastoma stem cells. In different pathways, cathepsins play a crucial role in processing functional proteins that are necessary for several processes and proper cell function...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28341864/microrna-140-5p-regulates-osteosarcoma-chemoresistance-by-targeting-hmgn5-and-autophagy
#13
Yichen Meng, Rui Gao, Jun Ma, Jianquan Zhao, Enjie Xu, Ce Wang, Xuhui Zhou
Chemotherapy is an important treatment modality for osteosarcoma. However, it often fails because of chemoresistance, especially multidrug resistance. Previously, we found several genes were involved in chemoresistance development. In this report, we used high-throughput microRNA (miRNA) expression analysis to reveal that expression of miR-140-5p was associated with chemosensitivity in osteosarcoma. The exact roles of miR-140-5p in the chemoresistance of osteosarcoma were then investigated, we found that knockdown of miR-140-5p enhanced osteosarcoma cells resistance to multiple chemotherapeutics while overexpression of miR-140-5p sensitized tumors to chemotherapy in vitro...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28294332/autophagy-mediates-cytotoxicity-of-human-colorectal-cancer-cells-treated-with-garcinielliptone-fc
#14
Shen-Jeu Won, Cheng-Hsin Yen, Ting-Yu Lin, Ya-Fen Jiang-Shieh, Chun-Nan Lin, Jyun-Ti Chen, Chun-Li Su
The tautomeric pair of garcinielliptone FC (GFC) is a novel tautomeric pair of polyprenyl benzophenonoid isolated from the pericarps of Garcinia subelliptica Merr. (G. subelliptica, Clusiaceae), a tree with abundant sources of polyphenols. Our previous report demonstrated that GFC induced apoptosis on various types of human cancer cell lines including chemoresistant human colorectal cancer HT-29 cells. In the present study, we observed that many autophagy-related genes in GFC-treated HT-29 cells were up- and down-regulated using a cDNA microarray containing oncogenes and kinase genes...
March 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28216370/targeting-autophagy-in-cancer-stem-cells-as-an-anticancer-therapy
#15
Yuanyuan Lei, Dan Zhang, Jin Yu, Hui Dong, Jianwei Zhang, Shiming Yang
Cancer stem cells (CSCs), which comprise a small proportion of total cancer cells, have special capacities for self-renewal, differentiation and tumor formation. Currently, CSCs are regarded as the major cause of the failure in anticancer therapy, such as chemoresistance and/or radioresistance, tumor recurrence and metastasis. Autophagy, a process of cellular self-digestion and response to stress, has a role in tumor formation and progression, and it may play a dual role in CSCs-related resistance to anticancer therapy...
May 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28197632/pgrmc1-dependent-autophagy-by-hyperoside-induces-apoptosis-and-sensitizes-ovarian-cancer-cells-to-cisplatin-treatment
#16
Xiaofei Zhu, Mingde Ji, Yue Han, Yuanyuan Guo, Wenqiang Zhu, Feng Gao, Xuewen Yang, Chunbing Zhang
Cisplatin treatment some times leads to chemoresistance, which is now acknowledged partially due to the inductive expression of progesterone receptor membrane component (PGRMC)1 in ovarian cancer cells. PGRMC1 enhances autophagy, activates cytochrome p450, and inveigles signaling pathways to promote cell survival and reduce the effect of drug treatments. In this study, we give first line evidence that hyperoside inhibits cell viability, triggers autophagy and apoptosis in ovarian cancer cell lines. Mechanistically, PGRMC1-dependent autophagy was utilized by hyperoside to induce apoptotic cell death...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28176874/cxcl12-cxcr4-axis-induced-mir-125b-promotes-invasion-and-confers-5-fluorouracil-resistance-through-enhancing-autophagy-in-colorectal-cancer
#17
Xinfeng Yu, Wenna Shi, Yuhang Zhang, Xiaohui Wang, Shiyue Sun, Zhiyu Song, Man Liu, Qiao Zeng, Shuxiang Cui, Xianjun Qu
The activation of CXCL12/CXCR4 axis is associated with potential progression of cancer, such as invasion, metastasis and chemoresistance. However, the underlying mechanisms of CXCL12/CXCR4 axis and cancer progression have been poorly explored. We hypothesized that miRNAs might be critical downstream mediators of CXCL12/CXCR4 axis involved in cancer invasion and chemoresistance in CRC. In human CRC cells, we found that the activation of CXCL12/CXCR4 axis promoted epithelial-mesenchymal transition (EMT) and concurrent upregulation of miR-125b...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28166203/lncrna-hulc-triggers-autophagy-via-stabilizing-sirt1-and-attenuates-the-chemosensitivity-of-hcc-cells
#18
H Xiong, Z Ni, J He, S Jiang, X Li, J He, W Gong, L Zheng, S Chen, B Li, N Zhang, X Lyu, G Huang, B Chen, Y Zhang, F He
Considerable evidences have shown that autophagy has an important role in tumor chemoresistance. However, it is still unknown whether the lncRNA HULC (highly upregulated in liver cancer) is involved in autophagy and chemoresistance of hepatocellular carcinoma (HCC). In this study, we for the first time demonstrated that treatment with antitumor reagents such as oxaliplatin, 5-fluorouracil and pirarubicin (THP) dramatically induced HULC expression and protective autophagy. Silencing of HULC sensitized HCC cells to the three antitumor reagents via inhibiting protective autophagy...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28147244/the-pi3k-inhibitor-gdc-0941-enhances-radiosensitization-and-reduces-chemoresistance-to-temozolomide-in-gbm-cell-lines
#19
Fei Shi, Hongchuan Guo, Rong Zhang, Hongyu Liu, Liangliang Wu, Qiyan Wu, Jialin Liu, Tianyi Liu, Qiuhang Zhang
Glioblastoma multiforme (GBM) is among the most lethal of all human tumors. It is the most frequently occurring malignant primary brain tumor in adults. The current standard of care (SOC) for GBM is initial surgical resection followed by treatment with a combination of temozolomide (TMZ) and ionizing radiation (IR). However, GBM has a dismal prognosis, and survivors have compromised quality of life owing to the adverse effects of radiation. GBM is characterized by overt activity of the phosphoinositide 3-kinase (PI3K) signaling pathway...
January 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28115426/p97-negatively-regulates-nrf2-by-extracting-ubiquitylated-nrf2-from-the-keap1-cul3-e3-complex
#20
Shasha Tao, Pengfei Liu, Gang Luo, Montserrat Rojo de la Vega, Heping Chen, Tongde Wu, Joseph Tillotson, Eli Chapman, Donna D Zhang
Activation of the stress-responsive transcription factor NRF2 is the major line of defense to combat oxidative or electrophilic insults. Under basal conditions, NRF2 is continuously ubiquitylated by the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex and is targeted to the proteasome for degradation (the canonical mechanism). However, the path from the CUL3 complex to ultimate proteasomal degradation was previously unknown. p97 is a ubiquitin-targeted ATP-dependent segregase that extracts ubiquitylated client proteins from membranes, protein complexes, or chromatin and has an essential role in autophagy and the ubiquitin proteasome system (UPS)...
April 15, 2017: Molecular and Cellular Biology
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