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Autophagy and chemotherapy resistance

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https://www.readbyqxmd.com/read/28545464/c10orf10-depp-mediated-ros-accumulation-is-a-critical-modulator-of-foxo3-induced-autophagy
#1
S Salcher, M Hermann, U Kiechl-Kohlendorfer, M J Ausserlechner, P Obexer
BACKGROUND: Neuroblastoma is the most common solid tumor in childhood and develops from undifferentiated progenitor cells of the sympathetic nervous system. In neuronal tumor cells DNA-damaging chemotherapeutic agents activate the transcription factor FOXO3 which regulates the formation of reactive oxygen species (ROS) and cell death as well as a longevity program associated with therapy resistance. We demonstrated before that C10ORF10/DEPP, a transcriptional target of FOXO3, localizes to peroxisomes and mitochondria and impairs cellular ROS detoxification...
May 25, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28536931/guanosine-promotes-cytotoxicity-via-adenosine-receptors-and-induces-apoptosis-in-temozolomide-treated-a172-glioma-cells
#2
Karen A Oliveira, Tharine A Dal-Cim, Flávia G Lopes, Cláudia B Nedel, Carla Inês Tasca
Gliomas are a malignant tumor group whose patients have survival rates around 12 months. Among the treatments are the alkylating agents as temozolomide (TMZ), although gliomas have shown multiple resistance mechanisms for chemotherapy. Guanosine (GUO) is an endogenous nucleoside involved in extracellular signaling that presents neuroprotective effects and also shows the effect of inducing differentiation in cancer cells. The chemotherapy allied to adjuvant drugs are being suggested as a novel approach in gliomas treatment...
May 23, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28531143/a-4-phenoxyphenol-derivative-exerts-inhibitory-effects-on-human-hepatocellular-carcinoma-cells-through-regulating-autophagy-and-apoptosis-accompanied-by-downregulating-%C3%AE-tubulin-expression
#3
Wen-Tsan Chang, Wangta Liu, Yi-Han Chiu, Bing-Hung Chen, Shih-Chang Chuang, Yen-Chun Chen, Yun-Tzh Hsu, Mei-Jei Lu, Shean-Jaw Chiou, Chon-Kit Chou, Chien-Chih Chiu
Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines...
May 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28524116/inhibition-of-autophagy-promotes-salinomycin-induced-apoptosis-via-reactive-oxygen-species-mediated-pi3k-akt-mtor-and-erk-p38-mapk-dependent-signaling-in-human-prostate-cancer-cells
#4
Kwang-Youn Kim, Kwang-Il Park, Sang-Hun Kim, Sun-Nyoung Yu, Sul-Gi Park, Young Woo Kim, Young-Kyo Seo, Jin-Yeul Ma, Soon-Cheol Ahn
Recently, the interplay between autophagy and apoptosis has become an important factor in chemotherapy for cancer treatment. Inhibition of autophagy may be an effective strategy to improve the treatment of chemo-resistant cancer by consistent exposure to chemotherapeutic drugs. However, no reports have clearly elucidated the underlying mechanisms. Therefore, in this study, we assessed whether salinomycin, a promising anticancer drug, induces apoptosis and elucidated potential antitumor mechanisms in chemo-resistant prostate cancer cells...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#5
Lin Wang, Justin H Gundelach, Richard J Bram
Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28508718/frondoside-a-induces-aif-associated-caspase-independent-apoptosis-in-burkitt-lymphoma-cells
#6
Sergey A Dyshlovoy, Stefanie Rast, Jessica Hauschild, Katharina Otte, Winfried H Alsdorf, Ramin Madanchi, Vladimir I Kalinin, Alexandra S Silchenko, Sergey A Avilov, Judith Dierlamm, Friedemann Honecker, Valentin A Stonik, Carsten Bokemeyer, Gunhild von Amsberg
For patients with refractory or relapsed Burkitt lymphoma (BL), no standard therapy is available for second-line treatment to date. Nonfunctional caspases-dependent apoptosis pathways, inactivating p53 mutations and pro-survival autophagy prevent activity of conventional chemotherapy. Thus, new drugs bypassing these mechanisms of resistance are required. Here, we investigated the efficacy of the marine natural compound frondoside A (FrA) in eight BL cell lines. FrA revealed cytotoxic effects in all cell lines tested including the multiresistant CA46 cells...
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28479604/codelivery-of-dihydroartemisinin-and-doxorubicin-in-mannosylated-liposomes-for-drug-resistant-colon-cancer-therapy
#7
Xue-Jia Kang, Hui-Yuan Wang, Hui-Ge Peng, Bin-Fan Chen, Wen-Yuan Zhang, Ai-Hua Wu, Qin Xu, Yong-Zhuo Huang
Multidrug resistance (MDR) is a major hurdle in cancer chemotherapy and makes the treatment benefits unsustainable. Combination therapy is a commonly used method for overcoming MDR. In this study we investigated the anti-MDR effect of dihydroartemisinin (DHA), a derivative of artemisinin, in combination with doxorubicin (Dox) in drug-resistant human colon tumor HCT8/ADR cells. We developed a tumor-targeting codelivery system, in which the two drugs were co-encapsulated into the mannosylated liposomes (Man-liposomes)...
May 8, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28465257/5-fluorouracil-targets-histone-acetyltransferases-p300-cbp-in-the-treatment-of-colorectal-cancer
#8
Changzheng Du, Dandan Huang, Yifan Peng, Yunfeng Yao, Ying Zhao, Yang Yang, Haiying Wang, Linlin Cao, Wei-Guo Zhu, Jin Gu
Although 5-fluorouracil (5-FU) is known to interfere with the synthesis of ribonucleic acid and deoxyribonucleic acid, the mechanism underlying its therapeutic efficacy in colorectal cancer (CRC) has not been fully elucidated. We aimed to investigate the influence of 5-FU on histone acetylation, a well-established anti-cancer target, to reveal novel pharmacological effects of 5-FU and their significance for CRC therapy. Results demonstrated that 5-FU induces global histone de-acetylation in multiple CRC cell lines...
April 29, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28459209/effects-of-endoplasmic-reticulum-stress-on-the-autophagy-apoptosis-and-chemotherapy-resistance-of-human-breast-cancer-cells-by-regulating-the-pi3k-akt-mtor-signaling-pathway
#9
Jia-Teng Zhong, Jian Yu, Hai-Jun Wang, Yu Shi, Tie-Suo Zhao, Bao-Xia He, Bin Qiao, Zhi-Wei Feng
Nowadays, although chemotherapy is an established therapy for breast cancer, the molecular mechanisms of chemotherapy resistance in breast cancer remain poorly understood. This study aims to explore the effects of endoplasmic reticulum stress on autophagy, apoptosis, and chemotherapy resistance in human breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the cell viability of six human breast cancer cell lines (MCF-7, ZR-75-30, T47D, MDA-MB-435s, MDA-MB-453, and MDA-MB-231) treated with tunicamycin (5 µM), after which MCF-7 cells were selected for further experiment...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28459042/autophagy-regulating-micrornas-and-cancer
#10
REVIEW
Devrim Gozuacik, Yunus Akkoc, Deniz Gulfem Ozturk, Muhammed Kocak
Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway that is responsible for the degradation of long-lived proteins, protein aggregates, as well as damaged organelles in order to maintain cellular homeostasis. Consequently, abnormalities of autophagy are associated with a number of diseases, including Alzheimers's disease, Parkinson's disease, and cancer. According to the current view, autophagy seems to serve as a tumor suppressor in the early phases of cancer formation, yet in later phases, autophagy may support and/or facilitate tumor growth, spread, and contribute to treatment resistance...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28455291/hyper-phosphorylation-of-sequestosome-1-distinguishes-resistance-to-cisplatin-in-patient-derived-high-grade-serous-ovarian-cancer-cells
#11
Elizabeth V Nguyen, Kaisa Huhtinen, Young Ah Goo, Katja Kaipio, Noora Andersson, Ville Rantanen, Johanna Hynninen, Riitta Lahesmaa, Olli Carpen, David R Goodlett
Platinum-resistance is a major limitation to effective chemotherapy regimens in high-grade serous ovarian cancer (HGSOC). To better understand the mechanisms involved we characterized the proteome and phosphoproteome in cisplatin sensitive and resistant HGSOC primary cells using a mass spectrometry-based proteomic strategy. PCA analysis identified a distinctive phosphoproteomic signature between cisplatin sensitive and resistant cell lines. The most phosphorylated protein in cisplatin resistant cells was sequestosome-1 (p62/SQSTM1)...
April 28, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28454274/role-of-endoplasmic-reticulum-stress-on-cisplatin-resistance-in-ovarian-carcinoma
#12
Jing Tian, Rong Liu, Quanxin Qu
Endoplasmic reticulum (ER) is an essential site of cellular homeostasis regulation. ER stress (ERS) may induce autophagy in tumor cells that escape from apoptosis. The present study examined the effects and mechanism of ERS on cisplatin (DDP) sensitivity in ovarian carcinoma. SKOV3 tumor cells treated with Saquinavir were subjected to western blot and reverse transcription-quantitative polymerase chain reaction analysis to determine protein and messenger RNA (mRNA) expression levels of mechanistic target of rapamycin (mTOR) and Beclin 1...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28445132/targeting-autophagic-cancer-stem-cells-to-reverse-chemoresistance-in-human-triple-negative-breast-cancer
#13
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)...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28438108/17-aag-and-apoptosis-autophagy-and-mitophagy-in-canine-osteosarcoma-cell-lines
#14
M Massimini, C Palmieri, R De Maria, M Romanucci, D Malatesta, M De Martinis, L Maniscalco, A Ciccarelli, L Ginaldi, P Buracco, L Bongiovanni, L Della Salda
Canine osteosarcoma is highly resistant to current chemotherapy; thus, clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) prototype of Hsp90 (heat shock protein 90) inhibitors in 2 canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy, and mitophagy, in light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0...
May 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28433739/dual-functional-drug-liposomes-in-treatment-of-resistant-cancers
#15
REVIEW
Li-Min Mu, Rui-Jun Ju, Rui Liu, Ying-Zi Bu, Jing-Ying Zhang, Xue-Qi Li, Fan Zeng, Wan-Liang Lu
Efficacy of regular chemotherapy is significantly hampered by multidrug resistance (MDR) and severe systemic toxicity. The reduced toxicity has been evidenced after administration of drug liposomes, consisting of the first generation of regular drug liposomes, the second generation of long-circulation drug liposomes, and the third generation of targeting drug liposomes. However, MDR of cancers remains as an unsolved issue. The objective of this article is to review the dual-functional drug liposomes, which demonstrate the potential in overcoming MDR...
April 20, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28415557/long-non-coding-rna-cta-sensitizes-osteosarcoma-cells-to-doxorubicin-through-inhibition-of-autophagy
#16
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...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404910/thalidezine-a-novel-ampk-activator-eliminates-apoptosis-resistant-cancer-cells-through-energy-mediated-autophagic-cell-death
#17
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...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401013/resistin-confers-resistance-to-doxorubicin-induced-apoptosis-in-human-breast-cancer-cells-through-autophagy-induction
#18
Zhenyu Liu, Aiping Shi, Dong Song, Bing Han, Zhiru Zhang, Le Ma, Dongxu Liu, Zhimin Fan
Clear evidence has linked obesity to a high risk of incidence as well as poor clinical outcome of breast cancer. It has been proven that changes in the levels of adipokines caused by obesity are associated with the initiation and progression of breast cancer. Resistin is a novel adipokine that is upregulated in breast cancer patients and promotes breast cancer cell growth, invasion, and migration. The aim of the study was to investigate whether resistin affected the efficacy of doxorubicin (Dox), one of the most effective anthracycline chemotherapeutic agents in the treatment of breast cancer...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28381160/insights-into-the-involvement-of-noncoding-rnas-in-5-fluorouracil-drug-resistance
#19
REVIEW
Jun Deng, Yi Wang, Jun Lei, Wan Lei, Jian Ping Xiong
5-Fluorouracil is a classic chemotherapeutic drug that is widely used to treat various cancers. However, patients often exhibit primary or acquired drug resistance during treatment with 5-fluorouracil chemotherapy. 5-Fluorouracil resistance is a multifactorial event that involves abnormal enzyme metabolism, transport deregulation, cell cycle disorders, apoptosis resistance, and mismatch repair deficiency. Despite advancements in bioresearch technologies in the past several decades, the molecular mechanisms of 5-fluorouracil resistance have not been completely clarified...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28379541/resistance-to-apoptosis-and-autophagy-leads-to-enhanced-survival-in-sertoli-cells
#20
Ferial Aslani, Tim Sebastian, Miguel Keidel, Suada Fröhlich, Hans-Peter Elsässer, Hans-Christian Schuppe, Jörg Klug, Poornima Mahavadi, Monika Fijak, Martin Bergmann, Andreas Meinhardt, Sudhanshu Bhushan
STUDY QUESTION: What is the underlying mechanism of Sertoli cell (SC) resistance to cell death? SUMMARY ANSWER: High expression of pro-survival B cell lymphoma-2 (BCL2) proteins and inhibition of apoptosis and autophagy prolongs SC survival upon exposure to stress stimuli. WHAT IS KNOWN ALREADY: In human and in experimental models of orchitis, tolerogenic SC survive stress conditions, while germ cells undergo massive apoptosis. In general, non-dividing highly differentiated cells tend to resist stress conditions for a longer time by favoring activation of pro-survival mechanisms and inhibition of cell death pathways...
April 3, 2017: Molecular Human Reproduction
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