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Autophagy and chemoresistance

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https://www.readbyqxmd.com/read/28906492/ndrg1-inhibition-sensitizes-osteosarcoma-cells-to-combretastatin-a-4-through-targeting-autophagy
#1
Hongsheng Wang, Wen Li, Jing Xu, Tao Zhang, Dongqing Zuo, Zifei Zhou, Binhui Lin, Gangyang Wang, Zhuoying Wang, Wei Sun, Mengxiong Sun, Shimin Chang, Zhengdong Cai, Yingqi Hua
Combretastatin A-4 (CA-4), a tubulin-depolymerizing agent, shows promising antitumor efficacy and has been under several clinical trials in solid tumors for 10 years. Autophagy has an important pro-survival role in cancer therapy, thus targeting autophagy may improve the efficacy of antitumor agents. N-myc downstream-regulated gene 1 (NDRG1) is a significant stress regulatory gene, which mediates cell survival and chemoresistance. Here we reported that CA-4 could induce cell-protective autophagy, and combination treatment of CA-4 and autophagy inhibitor chloroquine (CQ) exerted synergistic cytotoxic effect on human osteosarcoma (OS) cells...
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28899456/clc5-decreases-the-sensitivity-of-multiple-myeloma-cells-to-bortezomib-via-promoting-pro-survival-autophagy
#2
Huimin Zhang, Yuhui Pang, Chuanbao Ma, Jianying Li, Huaquan Wang, Zonghong Shao
Resistance to bortezomib (BZ) is the major problem that largely limits its clinical application in multiple myeloma treatment. In current study, we investigated whether ClC5, a member of the chloride channel family, involved in this process. The results of MTT assay showed that BZ treatment decreased cell viability in three multiple myeloma cell lines (ARH77, U266 and SKO-007), with the IC50 value of 2.83 nM, 4.37 nM and 1.91 nM, respectively. Moreover, BZ increased the conversion of LC3B-I to LC3B-II and expressions of Beclin-1 and ATG5, concomitantly with decreased p62 expression...
September 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28861639/repositioning-of-proton-pump-inhibitors-in-cancer-therapy
#3
REVIEW
Zhen-Ning Lu, Bing Tian, Xiu-Li Guo
Drug repositioning, as a smart way to exploit new molecular targets of a known drug, has been gaining increasing attention in the discovery of anti-cancer drugs. Proton pump inhibitors (PPIs) as benzimidazole derivatives, which are essentially H(+)-K(+)-ATPases inhibitors, are commonly used in the treatment of acid-related diseases such as gastric ulcer. In recent years, exploring the new application of PPIs in anti-cancer field has become a hot research topic. Interestingly, cancer cells display an alkaline intracellular pH and an acidic extracellular pH...
August 31, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28807161/phytochemical-modulation-of-apoptosis-and-autophagy-strategies-to-overcome-chemoresistance-in-leukemic-stem-cells-in-the-bone-marrow-microenvironment
#4
Helen C Owen, Sandra Appiah, Noor Hasan, Lucy Ghali, Ghada Elayat, Celia Bell
Advances in scientific research and targeted treatment regimes have improved survival rates for many cancers over the past few decades. However, for some types of leukemia, including acute lymphoblastic and acute myeloid leukemia, mortality rates have continued to rise, with chemoresistance in leukemic stem cells (LSCs) being a major contributing factor. Most cancer drug therapies act by inducing apoptosis in dividing cells but are ineffective in targeting quiescent LSCs. Niches in the bone marrow, known as leukemic niches, behave as "sanctuaries" where LSCs acquire drug resistance...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28797843/blockade-of-stearoyl-coa-desaturase-1-activity-reverts-resistance-to-cisplatin-in-lung-cancer-stem-cells
#5
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...
October 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28760781/mir-432-induces-nrf2-stabilization-by-directly-targeting-keap1
#6
Burak Akdemir, Yasuaki Nakajima, Johji Inazawa, Jun Inoue
NF-E2-related factor 2 (NRF2) is a master transcriptional regulator that integrates cellular stress responses and is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1) at the post-translational level. In human cancers, aberrantly stabilized NRF2, by the mutation of either NRF2 or KEAP1 or by the potential inhibition of autophagy, plays a vital role in tumor growth and chemoresistance through the activation of target genes. MicroRNAs (miRNAs) are endogenous small noncoding RNAs that can negatively regulate gene expression by interfering with translation and/or stability of target transcripts...
July 31, 2017: Molecular Cancer Research: MCR
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
#7
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/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/28726781/autophagy-inhibition-reduces-chemoresistance-and-tumorigenic-potential-of-human-ovarian-cancer-stem-cells
#9
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/28706161/the-molecular-mechanisms-of-chemoresistance-in-cancers
#10
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698397/hinokitiol-up-regulates-mir-494-3p-to-suppress-bmi1-expression-and-inhibits-self-renewal-of-breast-cancer-stem-progenitor-cells
#11
Shih-Ming Chen, Bing-Yen Wang, Che-Hsin Lee, Hsueh-Te Lee, Jung-Jung Li, Guan-Ci Hong, Yu-Chieh Hung, Peng-Ju Chien, Che-Ying Chang, Li-Sung Hsu, Wen-Wei Chang
Hinokitiol (β-thujaplicin) is a tropolone-related compound that has anti-microbe, anti-inflammation, and anti-tumor effects. Cancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells with tumor initiation, chemoresistant, and metastatic properties and have been considered the important therapeutic target in future cancer therapy. Previous studies reported that hinokitiol exhibits an anti-cancer activity against murine tumor cells through the induction of autophagy. The current research revealed that hinokitiol suppressed the self-renewal capabilities of human breast CSCs (BCSCs) and inhibited the expression of BMI1 at protein level without suppressing its mRNA...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28697598/nox2-mediated-tfeb-activation-and-vacuolization-regulate-lysosome-associated-cell-death-induced-by-gypenoside-l-a-saponin-isolated-from-gynostemma-pentaphyllum
#12
Kai Zheng, Yingchun Jiang, Chenghui Liao, Xiaopeng Hu, Yan Li, Yong Zeng, Jian Zhang, Xuli Wu, Haiqiang Wu, Lizhong Liu, Yifei Wang, Zhendan He
Downregulation of apoptotic signal pathway and activation of protective autophagy mainly contribute to the chemoresistance of tumor cells. Therefore, exploring efficient chemotherapeutic agents or isolating novel natural products that can trigger nonapoptotic and nonautophagic cell death such as lysosome-associated death is emergently required. We have recently extracted a saponin, gypenoside L (Gyp-L), from Gynostemma pentaphyllum and showed that Gyp-L was able to induce nonapoptotic cell death of esophageal cancer cells associated with lysosome swelling...
August 9, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28683561/ros-mediated-autophagy-defines-the-fate-of-cancer-stem-cells
#13
Matilde E Lleonart, Etna Abad, Dmitry Graifer, Alex Lyakhovich
SIGNIFICANCE: A fraction of tumorigenic cells, also known as tumor initiating or cancer stem cells, is thought to drive tumor growth, metastasis and chemoresistance. However, little is known regarding mechanisms that convey relevant pathways contributing to their self-renewal, proliferation and differentiation abilities. Recent Advances: Recent works on cancer stem cells provide evidence on the role of redox disruption and regulation of autophagic flux. This has been linked to increased DNA repair capacity and chemoresistance...
July 6, 2017: Antioxidants & Redox Signaling
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
#14
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
#15
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/28631572/endoplasmic-reticulum-stress-could-induce-autophagy-and-apoptosis-and-enhance-chemotherapy-sensitivity-in-human-esophageal-cancer-ec9706-cells-by-mediating-pi3k-akt-mtor-signaling-pathway
#16
Fang Zhou, Yan-Hua Li, Jian-Jun Wang, Jia Pan, Hong Lu
The study was designed to explore the mechanism of tunicamycin-induced endoplasmic reticulum stress in human esophageal cancer EC9706 cells and EC109 cells, as well as its effects on cell autophagy, apoptosis, and chemoresistance. Tunicamycin-induced endoplasmic reticulum stress model was established in EC9706 and EC109 cell lines. Western blotting was employed to detect the expression of endoplasmic reticulum stress iconic protein GRP78. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate the effect of different cisplatin and tunicamycin concentrations on survival rate of EC9706 cells and EC109 cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28605878/an-oasis-in-the-desert-of-cancer-chemotherapeutic-resistance-the-enlightenment-from-reciprocal-crosstalk-between-signaling-pathways-of-upr-and-autophagy-in-cancers
#17
REVIEW
Yuhang Zhang, Xianjun Qu, Lingfan Jiang
Endoplasmic reticulum (ER), principal but complex, functions as the pleiotropic organelle for proper protein folding, Ca(2+) storage as well as lipid and carbohydrate metabolisms. Diverse microenviromental insults including, but not limited to, inflammatory reaction, glucose imbalance and hypoxia, elicit the accumulation of potentially toxic unfolded proteins in the ER lumen. Under the condition of these cellular threats, the autophagy with the well-orchestrated program containing over 30 autophagy-related genes (ATGs) might be initiated for degrading and recycling of the cumulative misfolded proteins and other related abnormal cytoplasmic components...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28600513/trpc5-induced-autophagy-promotes-drug-resistance-in-breast-carcinoma-via-camkk%C3%AE-ampk%C3%AE-mtor-pathway
#18
Peng Zhang, Xiaoyu Liu, Hongjuan Li, Zhen Chen, Xiaoqiang Yao, Jian Jin, Xin Ma
Adriamycin is a first-line chemotherapy agent against cancer, but the development of resistance has become a major problem. Although autophagy is considered to be an adaptive survival response in response to chemotherapy and may be associated with chemoresistance, its inducer and the underlying molecular mechanisms remain unclear. Here, we demonstrate that adriamycin up-regulates the both levels of TRPC5 and autophagy, and the increase in autophagy is mediated by TRPC5 in breast cancer cells. Blockade of TRPC5 or autophagy increased the sensitivity to chemotherapy in vitro and in vivo...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592122/knockdown-of-cftr-enhances-sensitivity-of-prostate-cancer-cells-to-cisplatin-via-inhibition-of-autophagy
#19
Q Zhu, H Li, Y Liu, L Jiang
Prostate cancer is one of the most lethal diseases in men worldwide. Although the survival rate of men diagnosed with prostate cancer has increased with the improvement of treatments, drug resistance still remains a big challenge for improving overall survival. Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated anion channel, has been reported to have a pivotal role in the pathogenesis of various cancers, but its role in chemoresistance of prostate cancer cells is poorly understood...
June 8, 2017: Neoplasma
https://www.readbyqxmd.com/read/28592119/tea-polyphenol-inhibits-autophagy-to-sensitize-epirubicin-induced-apoptosis-in-human-bladder-cancer-cells
#20
W Gu, Y Lin, X Gou, W He
Resistance to anticancer agents such as Epirubicin (EPI) becomes a great challenge for treating bladder cancer. However, the mechanism by which chemoresistance arised is still elusive. In the present study, we showed evidence that EPI induced cytoprotective autophagy in bladder cancer cell lines T24 and BIU87. In addition, EPI robustly activated JNK-mediated phosphorylation of Bcl-2 and disruption of Bcl-2/Beclin-1 complex. Furthermore, the green tea derivative tea polyphenol (TP) inhibited EPI-induced autophagy and promoted apoptosis induced by EPI in bladder cancer cells...
June 8, 2017: Neoplasma
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