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Autophagy and chemotherapy resistance

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https://www.readbyqxmd.com/read/29322476/negative-regulators-of-cell-death-pathways-in-cancer-perspective-on-biomarkers-and-targeted-therapies
#1
REVIEW
Ali Razaghi, Kirsten Heimann, Patrick M Schaeffer, Spencer B Gibson
Cancer is a primary cause of human fatality and conventional cancer therapies, e.g., chemotherapy, are often associated with adverse side-effects, tumor drug-resistance, and recurrence. Molecularly targeted therapy, composed of small-molecule inhibitors and immunotherapy (e.g., monoclonal antibody and cancer vaccines), is a less harmful alternative being more effective against cancer cells whilst preserving healthy tissues. Drug-resistance, however, caused by negative regulation of cell death signaling pathways, is still a challenge...
January 10, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29312612/the-anti-cancer-effects-and-mechanisms-of-scutellaria-barbata-d-don-on-cl1-5-lung-cancer-cells
#2
Chin-Chuan Chen, Chun-Pin Kao, Mei-Miao Chiu, Shu-Huei Wang
Lung cancer, with a poor prognosis and resistance to chemotherapy, is the most common malignant tumor and has the highest mortality rate worldwide. Scutellaria barbata D. Don (SB), which is derived from the dried whole plant of Labiatae, is a well-known anti-inflammatory and anti-cancer herb. The aim of this study was to examine the anti-cancer effects and precise regulatory mechanisms of SB in CL1-5 lung cancer cells. In an in vitro assay, we found that the anti-tumor mechanism of SB was due to P38/SIRT1-regulated cell apoptosis through G2/M phase arrest and ER stress-, intrinsic mitochondrial-, and extrinsic FAS/FASL-mediated pathways...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29306018/aldehyde-dehydrogenase-1a3-aldh1a3-is-regulated-by-autophagy-in-human-glioblastoma-cells
#3
Wei Wu, Johannes Schecker, Sylvia Würstle, Fabian Schneider, Martin Schönfelder, Jürgen Schlegel
Aldehyde dehydrogenase is a polymorphic enzyme, which responsible for the oxidation of aldehydes. It has been shown that ALDH1A3 is expressed in human glioblastomas and that its expression correlates with a worse prognosis. In our present study ALDH1A3 expression was associated with resistance against Temozolomide (TMZ) treatment and sensitivity could be re-established in ALDH1A3 knockout cells. TMZ treatment at high concentrations diminished ALDH1A3 protein and this downregulation made the tumor cells more sensitive to chemotherapy...
January 3, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29296226/annexin-a4-fucosylation-enhances-its-interaction-with-the-nf-kb-p50-and-promotes-tumor-progression-of-ovarian-clear-cell-carcinoma
#4
Huimin Wang, Lu Deng, Mingbo Cai, Huiyu Zhuang, Liancheng Zhu, Yingying Hao, Jian Gao, Juanjuan Liu, Xiao Li, Bei Lin
Objective: To study the structural relationship between annexin A4 and the Lewis y antigen and compare their expression and significance in ovarian clear cell carcinoma, and to explore how annexin A4 fucose glycosylation effects the interaction between annexin A4 and NF-kB p50, and how it promotes tumour progression of ovarian clear cell carcinoma. Methods: Structural relationships between annexin A4 and Lewis y antigen were detected using immunoprecipitation. Annexin A4 and Lewis y antigen expression in various subtypes of ovarian cancer tissues was detected by immunohistochemistry, and the relation between their expression was examined...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296182/microrna-410-3p-attenuates-gemcitabine-resistance-in-pancreatic-ductal-adenocarcinoma-by-inhibiting-hmgb1-mediated-autophagy
#5
Junjie Xiong, Dan Wang, Ailin Wei, Nengwen Ke, Yichao Wang, Jie Tang, Sirong He, Weiming Hu, Xubao Liu
Gemcitabine-based chemotherapy is the most common treatment option for pancreatic ductal adenocarcinoma (PDAC). However, it offers little therapeutic value in many cases due to the rapid development of chemoresistance. MicroRNAs (miRNAs) have been found to play pivotal roles in the chemotherapeutic resistance of PDAC. We found that miR-410-3p was significantly down-regulated in human pancreatic cancer xenograft (HPCx) tumor tissues from gemcitabine-treated mice. Low miR-410-3p expression correlated with gemcitabine resistance in HPCx tumors and PDAC cells as well as poor prognosis in PDAC patients...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295727/mirna-409-3p-enhances-cisplatin-sensitivity-of-ovarian-cancer-cells-by-blocking-the-autophagy-mediated-by-fip200
#6
Yue Cheng, Runwu Ban, Wei Liu, Hongzhi Wang, Shuzhi Li, Zhenfei Yue, Gang Zhu, Yuan Zhuan, Changjuan Wang
Background: Efficacy of chemotherapy for ovarian cancer (OC) is usually affected by various factors,especially the chemoresistance of ovarian cancer cells. Downregulation of miR-409-3p has been found in a variety of tumors. However, the role of miR-409-3p in chemo-resistant OC cells still remains unknown. The aim of this study was to investigate the effect of miR-409-3p on cisplatin-resistant OC cells and to elucidate the mechanism by which enhances cisplatin-sensitivity of OC cells. Methods: Expression of miR-409-3p in OC cells was assessed by qRT-PCR...
January 2, 2018: Oncology Research
https://www.readbyqxmd.com/read/29290796/prlz-increases-prostate-cancer-docetaxel-resistance-by-inhibiting-lkb1-ampk-mediated-autophagy
#7
Jin Zeng, Wei Liu, Yi-Zeng Fan, Da-Lin He, Lei Li
Rationale: Docetaxel-mediated chemotherapy is the first-line standard approach and has been determined to show a survival advantage for metastatic castration-resistant prostate cancer (mCRPC) patients. However, a substantial proportion of patients eventually becomes refractory due to drug resistance. The detailed mechanisms remain unclear. We have previously reported that Prostate Leucine Zipper (PrLZ), a specific oncogene of prostate cancer (PCa), promotes PCa cell growth at the castration-resistant stage, thus suggesting a vital role of PrLZ in the progression of CRPC...
2018: Theranostics
https://www.readbyqxmd.com/read/29277783/up-regulation-of-uvrag-by-hdac1-inhibition-attenuates-5fu-induced-cell-death-in-hct116-colorectal-cancer-cells
#8
Yoon Kyung Jo, Na Yeon Park, Ji Hyun Shin, Doo Sin Jo, Ji-Eun Bae, Eun Sun Choi, Sungho Maeng, Hong Bae Jeon, Seon Ae Roh, Jong Wook Chang, Jin Cheon Kim, Dong-Hyung Cho
The ultraviolent irradiation resistance-associated gene (UVRAG), a component of the Beclin 1/autophagy-related 6 complex, regulates the autophagy initiation step and functions in the DNA-damage response. UVRAG is frequently mutated in various cancer types, and mutations of UVRAG increase sensitivity to chemotherapy by impairing DNA-damage repair. In this study, we addressed the epigenetic regulation of UVRAG in colorectal cancer cells. UVRAG expression was increased in cells treated with histone deacetylase (HDAC) inhibitors, such as valproic acid and suberoylanilide hydroxamic acid...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29246644/docetaxel-mediated-autophagy-promotes-chemoresistance-in-castration-resistant-prostate-cancer-cells-by-inhibiting-stat3
#9
Fei Hu, Yu Zhao, Yi Yu, Jue-Min Fang, Ran Cui, Zhu-Qing Liu, Xian-Ling Guo, Qing Xu
Signal transducer and activator of transcription (STAT)3 expression is correlated with neoplasm growth, metastasis, and prognosis; it has also been implicated in the regulation of autophagy, which may in turn contribute to tumor chemoresistance. However, it is unknown whether STAT3 is involved in cancer cell survival in response to chemotherapy. In this study, we show that autophagy is triggered during chemotherapy and that inhibiting autophagy increased chemosensitivity of castration-resistant prostate cancer (CRPC) cells...
December 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29246220/inhibition-of-autophagy-enhances-synergistic-effects-of-salidroside-and-anti-tumor-agents-against-colorectal-cancer
#10
Hai Li, Chen Chen
BACKGROUND: Various plant extracts have been suggested to be used as auxiliary agents in chemotherapy considering their anti-proliferative effect on cancer cells. However, recent reports reveal that plant extracts may function as inducers of autophagy of cancer cells. In general, autophagy confers survival advantage for cells responding to stress conditions, thus representing an important mechanism for chemo-resistance. This study was aimed to investigate the effectiveness of combined use of Salidroside (Sal, a phenylpropanoid glycosides from Rhodiola rosea L) with anti-tumor agents against colorectal cancer (CRC) cells, and moreover to evaluate the potential role of autophagy in the combined therapy...
December 16, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29236768/autophagy-induction-by-mycobacterium-indicus-pranii-promotes-mycobacterium-tuberculosis-clearance-from-raw-264-7-macrophages
#11
Bindu Singh, Mohd Saqib, Ananya Gupta, Pawan Kumar, Sangeeta Bhaskar
Mycobacterium indicus pranii (MIP) is a potent vaccine candidate against tuberculosis (TB) as it has demonstrated significant protection in animal models of tuberculosis as well as in clinical trials. Higher protective efficacy of MIP against TB as compared to BCG provoked the efforts to gain insight into the molecular mechanisms underlying MIP mediated protection against Mycobacterium tuberculosis (M.tb). Autophagy, initially described as a cell survival mechanism during starvation, also plays a key role in host resistance to M...
2017: PloS One
https://www.readbyqxmd.com/read/29201061/selective-and-irreversible-induction-of-necroptotic-cell-death-in-lung-tumorspheres-by-short-term-exposure-to-verapamil-in-combination-with-sorafenib
#12
Juan Sebastian Yakisich, Yogesh Kulkarni, Neelam Azad, Anand Krishnan V Iyer
The presence of highly resistant cancer cells and the toxicity to normal cells are key factors that limit chemotherapy. Here, we used two models of highly resistant lung cancer cells: (1) adherent cells growing under prolonged periods of serum starvation (PPSS) and (2) cells growing as floating tumorspheres (FTs) to evaluate the effect of Verapamil (VP) in combination with Sorafenib (SF). Compared to cells growing under routine culture conditions (RCCs), PPPS cells or FTs were highly sensitive to short-term exposure (24 h) to VP 100 μM + SF 5 μM (VP100 + SF5)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29177673/hsp70-a-cancer-target-inside-and-outside-the-cell
#13
Christophe Boudesco, Sebastien Cause, Gaëtan Jego, Carmen Garrido
Heat shock protein 70 (Hsp70) is the most ubiquitous stress-inducible chaperone. It accumulates in the cells in response to a wide variety of physiological and environmental insults including anticancer chemotherapy, thus allowing the cell to survive to lethal conditions. Intracellular Hsp70 is viewed as a cytoprotective protein. Indeed, this protein can inhibit key effectors of the apoptotic and autophagy machineries. In cancer cells, the expression of Hsp70 is abnormally high, and Hsp70 may participate in oncogenesis and in resistance to chemotherapy...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29156523/cancer-associated-%C3%AF-broblasts-confer-cisplatin-resistance-of-tongue-cancer-via-autophagy-activation
#14
Juan-Kun Liao, Bin Zhou, Xiu-Mei Zhuang, Pei-Lin Zhuang, Da-Ming Zhang, Wei-Liang Chen
Cancer-associated fibroblasts (CAFs) play important roles in carcinogenesis and progression of tongue squamous cell carcinoma (TSCC). However, effect of CAFs on chemotherapy resistance of TSCC remains largely obscure. Here, we cultured the matched primary CAFs and normal fibroblasts (NFs) pairs and detected their roles in cisplatin sensitivity of TSCC, as well as autophagy-related protein LC3 and Beclin1 expressions. During exposure to cisplatin, TSCC with CAFs group exhibited significantly increased cell viability and IC50, but reduced apoptosis than that with NFs group...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29141550/autophagy-as-a-potential-therapeutic-target-in-breast-cancer-treatment
#15
Natalia Lisiak, Ewa Toton, Maria Rybczynska
One of the crucial reasons of breast cancer therapy failure is an impairment of mechanisms responsible for metabolism and cellular homeostasis, which makes it difficult to foresee the response to the treatment. Targeted therapy in breast cancer is dictated by the expression of specific molecules such as growth factor or hormone receptors. Many types of breast cancer exhibit different abnormalities in the apoptotic pathway, which confer the resistance to many forms of chemotherapy. Because of the fundamental importance of autophagy in the development and progression of cancer and its ability to affect treatment response, there has been an immense research on molecular regulation and signal transduction mechanisms that control this process...
November 14, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29130967/endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reduces-chemotherapy-resistance-in-mutant-p53-lung-cancer-cells
#16
Ping-Ping Gan, Yang-Ying Zhou, Mei-Zuo Zhong, Yun Peng, Li Li, Jian-Huang Li
BACKGROUND/AIMS: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. METHODS: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53)...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29130102/knockdown-of-lncrna-xist-enhances-the-chemosensitivity-of-nsclc-cells-via-suppression-of-autophagy
#17
Wei Sun, Yukun Zu, Xiangning Fu, Yu Deng
Drug resistance is the major factor contributing to the failure of chemotherapy in non-small cell lung cancer (NSCLC) patients. Emerging evidence suggests that autophagy plays a vital role in the chemoresistance of many types of tumors. However, the exact mechanism underlying the chemoresistance of NSCLC is still elusive, and it is unclear whether lncRNA-XIST is involved in autophagy and chemoresistance of NSCLC. In the present study, we demonstrated that lncRNA-XIST was overexpressed in NSCLC tumor samples, and knockdown of lncRNA-XIST significantly decreased autophagy by regulation of ATG7 as determined by qPCR and by western blotting...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29113279/hmgb1-mediated-autophagy-confers-resistance-to-gemcitabine-in-hormone-independent-prostate-cancer-cells
#18
Yi-Xiang Zhang, Ye-Qing Yuan, Xue-Qi Zhang, Dong-Long Huang, Yu-Ying Wei, Jiang-Gen Yang
As a main treatment of prostate cancer, castration therapy has been widely applied in the clinic. However, the therapeutic strategy for hormone-independent prostate cancer (HIPC) was not satisfied. Gemcitabine is an important chemotherapeutic agent that has been approved for the treatment of numerous human solid tumors, including HIPC, whereas the gemcitabine resistance has become a serious problem in clinical chemotherapy. In the present study, the mechanisms of resistance to gemcitabine were investigated in HIPC cell lines...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29107112/the-emerging-role-of-exosome-derived-non-coding-rnas-in-cancer-biology
#19
Qing Fan, Liang Yang, Xiaodong Zhang, Xueqiang Peng, Shibo Wei, Dongming Su, Zhenhua Zhai, Xiangdong Hua, Hangyu Li
Exosomes are a new means of intercellular information exchange that have aroused great research interest. Long neglected in research, exosomes were deemed nonfunctional cellular components to be discarded. However, it has been gradually revealed that exosomes are an important tool for the exchange of intercellular information and material. Exosomes contain specific repertoires of non-coding RNAs (ncRNAs, including microRNA and lncRNA), indicating that a specific RNA sorting mechanism may exist. Correspondingly, intracellular multivesicular bodies (MVBs) are produced after fusion with the cell membrane to release exosomes rather than inducing autophagy, which reveals that there may be a specific regulatory mechanism for MVB secretion...
October 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29101806/tetrandrine-and-cancer-an-overview-on-the-molecular-approach
#20
REVIEW
Bhagya N, Chandrashekar K R
Tetrandrine has been known in the treatment of tuberculosis, hyperglycemia, negative ionotropic and chronotropic effects on myocardium, malaria, cancer and fever since years together. It has been known that, tetrandrine could modulate multiple signaling molecules such as kinases of cell cycle and rat sarcoma (RAS) pathway along with proteins of tumor suppressor genes, autophagy related, β-catenins, caspases, and death receptors. Moreover, tetrandrine exhibited reversal of drug resistance by modulating P-glyco protein (P-gp) expression levels in different cancers which is an added advantage of this compound compared to other chemotherapy drugs...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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