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Autophagy and chemotherapy resistance

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https://www.readbyqxmd.com/read/29141550/autophagy-as-a-potential-therapeutic-target-in-breast-cancer-treatment
#1
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
#2
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
#3
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
#4
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
#5
Qing Fan, Shibo Wei, Liang Yang, Xiaodong Zhang, Xueqiang Peng, 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
#6
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
https://www.readbyqxmd.com/read/29098039/similarity-in-the-functions-of-hif-1%C3%AE-and-hif-2%C3%AE-proteins-in-cervical-cancer-cells
#7
Lixia Jiang, Shaohua Shi, Qiaofa Shi, Huijuan Zhang, Rong Hu, Meizhen Wang
Hypoxia is a common feature of many solid tumours, including cervical cancer. Aggressive tumour progression is mostly associated with hypoxia. Furthermore, hypoxic conditions in tumours are also associated with resistance to chemotherapy and radiation, and with poor prognosis. Hypoxia inducible factor (HIF)-1, composed of a constitutively expressed β-subunit (HIF-β/ARNT) and one of the three known oxygen-regulated α-subunits, HIF-1α, HIF-2α, or HIF-3α, mediates the tumour cell response to hypoxia. The distinction between the roles of HIF-1α and HIF-2α in tumorigenesis is not clearly delineated...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29074104/the-cycloartane-triterpenoid-adcx-impairs-autophagic-degradation-through-akt-overactivation-and-promotes-apoptotic-cell-death-in-multidrug-resistant-hepg2-adm-cells
#8
Haiyan Sun, Maohua Huang, Nan Yao, Jianyang Hu, Yingjie Li, Liping Chen, Nan Hu, Wencai Ye, William Chi-Shing Tai, Dongmei Zhang, Sibao Chen
Multidrug resistance is the main obstacle in cancer chemotherapy. Emerging evidence demonstrates the important role of autophagy in cancer cell resistance to chemotherapy. Therefore, autophagy inhibition by natural compounds may be a promising strategy for overcoming drug resistance in liver cancer cells. Here, we found that ADCX, a natural cycloartane triterpenoid extracted from the traditional Chinese medicine (TCM) source Cimicifugae rhizoma (Shengma), impaired autophagic degradation by suppressing lysosomal cathepsin B (CTSB) expression in multidrug-resistant liver cancer HepG2/ADM cells, thereby leading to autophagic flux inhibition...
October 23, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29050305/calyxin-y-sensitizes-cisplatin-sensitive-and-resistant-hepatocellular-carcinoma-cells-to-cisplatin-through-apoptotic-and-autophagic-cell-death-via-scf-%C3%AE-trcp-mediated-eef2k-degradation
#9
Chao Zhang, Jian-Li Lei, Hao Zhang, Yuan-Zheng Xia, Pei Yu, Lei Yang, Ling-Yi Kong
The down-regulation of eukaryotic elongation factor-2 kinase (eEF2K) is associated with an enhancement in the sensitivity of malignant cells to chemotherapeutic agents. In this study, we found that the silencing of eEF2K enhanced cisplatin (CDDP)-induced cytotoxicity in CDDP-sensitive (HepG2) and resistant (HepG2/CDDP) cells. Calyxin Y, a unique chalcone diarylheptanoid adduct, down-regulated eEF2K by promoting Skp1-Cul1-F-box protein (SCF) β-transducin repeat-containing protein (βTrCP)-mediated protein degradation and synergistically enhanced the cytotoxicity of CDDP...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048624/liquiritin-induces-apoptosis-and-autophagy-in-cisplatin-ddp-resistant-gastric-cancer-cells-in-vitro-and-xenograft-nude-mice-in-vivo
#10
Feng Wei, Xin Jiang, Hao-Yue Gao, Shuo-Hui Gao
Gastric cancer is reported as one of the leading factors resulting in tumor-related death worldwide. However, the therapies to suppress gastric cancer are still limited and the emergence of drug resistance makes it necessary to develop new and effective anticancer drugs and combinational chemotherapy schemes. Liquiritin (LIQ) is a major constituent of Glycyrrhiza Radix, exhibiting various pharmacological activities, including anticancer. In this study, we investigated the role of LIQ in human gastric cancer cells with cisplatin (DDP) resistance...
September 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29034071/apigenin-in-cancer-therapy-anti-cancer-effects-and-mechanisms-of-action
#11
REVIEW
Xiaohui Yan, Miao Qi, Pengfei Li, Yihong Zhan, Huanjie Shao
Apigenin is a common dietary flavonoid that is abundantly present in many fruits, vegetables and Chinese medicinal herbs and serves multiple physiological functions, such as strong anti-inflammatory, antioxidant, antibacterial and antiviral activities and blood pressure reduction. Therefore, apigenin has been used as a traditional medicine for centuries. Recently, apigenin has been widely investigated for its anti-cancer activities and low toxicity. Apigenin was reported to suppress various human cancers in vitro and in vivo by multiple biological effects, such as triggering cell apoptosis and autophagy, inducing cell cycle arrest, suppressing cell migration and invasion, and stimulating an immune response...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29027991/n6-isopentenyladenosine-dual-targeting-of-ampk-and-rab7-prenylation-inhibits-melanoma-growth-through-the-impairment-of-autophagic-flux
#12
Roberta Ranieri, Elena Ciaglia, Giuseppina Amodio, Paola Picardi, Maria Chiara Proto, Patrizia Gazzerro, Chiara Laezza, Paolo Remondelli, Maurizio Bifulco, Simona Pisanti
Targeting the autophagic process is considered a promising therapeutic strategy in cancer since a great number of tumors, including melanoma, show high basal levels of protective autophagy that contributes to tumor progression and chemoresistance. Here, exploiting both in vitro and in vivo approaches, we identified N6-isopentenyladenosine (iPA), an end product of the mevalonate pathway, as a novel autophagy inhibitor with an interesting anti-melanoma activity. iPA, after being phosphorylated by adenosine kinase into 5'-iPA-monophosphate, induces autophagosome accumulation through AMPK activation, measured by increased fluorescent GFP-LC3 puncta and enhanced conversion into the lipidated autophagosome-associated LC3-II...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29017913/the-use-of-natural-compounds-for-the-targeting-and-chemoprevention-of-ovarian-cancer
#13
Francesca Pistollato, Ruben Calderón Iglesias, Roberto Ruiz, Silvia Aparicio, Jorge Crespo, Luis Dzul Lopez, Francesca Giampieri, Maurizio Battino
Among gynaecological cancers, ovarian cancer represents the leading cause of death in women. Current treatment for ovarian cancer entails surgery followed by combined chemotherapy with platinum and taxane, which are associated, particularly cisplatin, with severe side effects. While this treatment approach appears to be initially effective in a high number of patients, nearly 70% of them suffer a relapse within a few months after initial treatment. Therefore, more effective and better-tolerated treatment options are clearly needed...
October 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28987049/downregulation-of-cohesin-loading-factor-nipped-b-like-protein-nipbl-induces-cell-cycle-arrest-apoptosis-and-autophagy-of-breast-cancer-cell-lines
#14
Huanhuan Zhou, Lei Zheng, Kongbeng Lu, Yun Gao, Liwei Guo, Weizhen Xu, Xiaojia Wang
BACKGROUND The cohesin loading factor, nipped-B-like protein (NIPBL), is also known as the sister chromatid cohesion 2 (SCC2) human homolog. Recently, we have studied the role of expression levels of NIPBL in cell proliferation and chemotherapy resistance of non-small cell lung cancer (NSCLC) cells in vitro. The aim of this study was to investigate the effects of expression of the cohesin loading factor, NIPBL, on the cell cycle, apoptosis, and autophagy of breast cancer cell lines in vitro. MATERIAL AND METHODS Expression levels of the NIPBL in the breast cancer cell lines, MCF7, Bcap37, MDA-MB 453 and MDA-MB 231, were measured using Western blot and flow cytometry...
October 7, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28978341/mab-mdr1-modified-chitosan-nanoparticles-overcome-acquired-egfr-tki-resistance-through-two-potential-therapeutic-targets-modulation-of-mdr1-and-autophagy
#15
Yan Zheng, Chang Su, Liang Zhao, Yijie Shi
BACKGROUND: Tyrosine kinase inhibitors (TKIs) that act against the epithelial growth factor receptor (EGFR) were once widely used in chemotherapy for many human cancers. However, acquired chemoresistance occurred in almost all patients, limiting the clinical application of EGFR-TKI. Thus far, no effective methods existing can resolve this problem. Designing a therapeutic treatment with a specific multi-target profile has been regarded as a possible strategy to overcome acquired EGFR-TKI resistance...
October 4, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28977849/endoplasmic-reticulum-stress-induces-autophagy-and-apoptosis-while-inhibiting-proliferation-and-drug-resistance-in-multiple-myeloma-through-the-pi3k-akt-mtor-signaling-pathway
#16
Yun-Feng Fu, Xiao Liu, Meng Gao, Ya-Nan Zhang, Jing Liu
We investigated the effects of endoplasmic reticulum stress (ERS) on autophagy, proliferation, apoptosis, and drug resistance in multiple myeloma (MM). MM patients enrolled in our study (n = 268) were classified into sensitive and resistant groups based on chemotherapy efficacy, and their serum levels of β2-MG, albumin (ALB), lactic dehydrogenase (LDH), Ca(2+) and hemoglobin were determined. In addition, human MM U266 and MOLP-2/R cells were divided into blank, tunicamycin (TM), TM + insulin-like growth factor-1 (IGF-1), and TM + rapamycin groups, and measured expression of ERS-related, PI3K/Akt/mTOR pathway-related, and autophagy-related mRNA and proteins...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977798/intensified-beclin-1-mediated-by-low-expression-of-mir-30a-5p-promotes-chemoresistance-in-human-small-cell-lung-cancer
#17
Xiang Yang, Fan Bai, Yichen Xu, Yitian Chen, Longbang Chen
BACKGROUND/AIMS: Although small cell lung cancer (SCLC) is sensitive to initial chemotherapy, patients experience tumor recurrence and metastasis, leading to treatment failure. Autophagy as a protective pattern for cell survival in the harsh environment plays an important role in chemoresistance. However, the role of Beclin-1, a key regulator of autophagy in the drug-resistance of SCLC cells is still poorly understood. In the current study, we focused on the effect and regulation of Beclin-1 in chemoresistance of SCLC cells...
October 5, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28965855/microrna-148a-3p-enhances-cisplatin-cytotoxicity-in-gastric-cancer-through-mitochondrial-fission-induction-and-cyto-protective-autophagy-suppression
#18
Bowen Li, Weizhi Wang, Zheng Li, Zheng Chen, Xiaofei Zhi, Jianghao Xu, Qing Li, Lu Wang, Xiaoxu Huang, Linjun Wang, Song Wei, Guangli Sun, Xuan Zhang, Zhongyuan He, Lu Zhang, Diancai Zhang, Hao Xu, Wael El-Rifai, Zekuan Xu
Cisplatin (CDDP) resistance is a major clinical problem associated with poor prognosis in gastric cancer (GC) patients. In this study, we performed integrated analysis of TCGA data from microRNAs (miRNAs) expression matrix of GC patients who received CDDP-based chemotherapy with GEO dataset which contains differential miRNAs expression profiles in CDDP-resistant and -sensitive cell lines. We identified miR-148a-3p downregulation as a key step involved in CDDP resistance. Using a cohort consisting 105 GC patients who received CDDP-based therapy, we found that miR-148a-3p downregulation was associated with a decrease in patients' disease-free survival (DFS, P = 0...
December 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28954454/autophagy-inhibition-increased-the-anti-tumor-effect-of-cisplatin-on-drug-resistant-esophageal-cancer-cells
#19
C Y Cheng, J C Liu, J J Wang, Y H Li, J Pan, Y R Zhang
The sensitivity of tumor cells to treatment can be affected by autophagy. The drug resistance of esophageal cancer cells against cisplatin occurs during the long period of chemotherapy drug treatment. This study was designed to observe the effect autophagy has on the occurrence of esophageal cancer cell drug resistance against cisplatin and investigate its molecular mechanism in order to provide new details and strategies for the clinical treatment of esophageal cancer, especially cisplatin treatment. The detection methods used in this study were 3-(4,5-dimethylthiazd-2-yl)-2,5-dipheny-ltetrazolium bromide (MTT) colorimetric assay, clone survival technique, small interfering RNA (siRNA) transfection, and Western blot...
July 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28936522/a-novel-hif-1%C3%AE-vmp1-autophagic-pathway-induces-resistance-to-photodynamic-therapy-in-colon-cancer-cells
#20
M E Rodríguez, C Catrinacio, A Ropolo, V A Rivarola, M I Vaccaro
Colon cancer is the third most frequent cancer and the fourth most common cause of cancer-related mortality worldwide and the standard therapy is surgical resection plus adjuvant chemotherapy. Photodynamic therapy (PDT) has been proposed as an adjuvant therapy because it can prevent the tumor recurrence after surgical excision in colon cancer patients. Hypoxia is a common feature in solid tumors and leads to chemo/radioresistance. Recently, it has been shown that in response to hypoxia, cells can induce HIF-1α-mediated autophagy to survive in this hostile microenvironment...
November 8, 2017: Photochemical & Photobiological Sciences
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