Serveur d'exploration Chloroquine

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Immunomodulatory proteins FIP-gts and chloroquine induce caspase-independent cell death via autophagy for resensitizing cisplatin-resistant urothelial cancer cells.

Identifieur interne : 000189 ( PubMed/Corpus ); précédent : 000188; suivant : 000190

Immunomodulatory proteins FIP-gts and chloroquine induce caspase-independent cell death via autophagy for resensitizing cisplatin-resistant urothelial cancer cells.

Auteurs : I-Lun Hsin ; Shao-Chuan Wang ; Jian-Ri Li ; Tsai-Chun Ciou ; Chih-Hsien Wu ; Hung-Ming Wu ; Jiunn-Liang Ko

Source :

RBID : pubmed:27823620

English descriptors

Abstract

Chloroquine, a lysosomal inhibitor, is used for malaria, rheumatoid arthritis, and lupus erythematosus therapy. In our previous study, FIP-gts, an immunomodulatory protein from Ganoderma tsugae, inhibited cell viability in lung cancer cells and urothelial cancer cells. Urothelial carcinoma is the most common type of bladder cancer. Cisplatin resistance is an important issue in urothelial carcinoma therapy.

DOI: 10.1016/j.phymed.2016.09.003
PubMed: 27823620

Links to Exploration step

pubmed:27823620

Le document en format XML

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<term>Amino Acid Chloromethyl Ketones (pharmacology)</term>
<term>Antineoplastic Combined Chemotherapy Protocols (pharmacology)</term>
<term>Apoptosis (drug effects)</term>
<term>Autophagy (drug effects)</term>
<term>Caspases (metabolism)</term>
<term>Cell Cycle (drug effects)</term>
<term>Cell Line, Tumor</term>
<term>Cell Survival (drug effects)</term>
<term>Chloroquine (administration & dosage)</term>
<term>Chloroquine (pharmacology)</term>
<term>Cisplatin (pharmacology)</term>
<term>Drug Resistance, Neoplasm (drug effects)</term>
<term>Fungal Proteins (administration & dosage)</term>
<term>Fungal Proteins (pharmacology)</term>
<term>Ganoderma (chemistry)</term>
<term>Humans</term>
<term>Immunologic Factors (pharmacology)</term>
<term>Membrane Potential, Mitochondrial (drug effects)</term>
<term>Urologic Neoplasms (drug therapy)</term>
<term>Urologic Neoplasms (pathology)</term>
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<term>Chloroquine</term>
<term>Fungal Proteins</term>
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<term>Caspases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Amino Acid Chloromethyl Ketones</term>
<term>Chloroquine</term>
<term>Cisplatin</term>
<term>Fungal Proteins</term>
<term>Immunologic Factors</term>
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<term>Ganoderma</term>
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<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Apoptosis</term>
<term>Autophagy</term>
<term>Cell Cycle</term>
<term>Cell Survival</term>
<term>Drug Resistance, Neoplasm</term>
<term>Membrane Potential, Mitochondrial</term>
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<term>Urologic Neoplasms</term>
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<div type="abstract" xml:lang="en">Chloroquine, a lysosomal inhibitor, is used for malaria, rheumatoid arthritis, and lupus erythematosus therapy. In our previous study, FIP-gts, an immunomodulatory protein from Ganoderma tsugae, inhibited cell viability in lung cancer cells and urothelial cancer cells. Urothelial carcinoma is the most common type of bladder cancer. Cisplatin resistance is an important issue in urothelial carcinoma therapy.</div>
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<Day>05</Day>
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<ArticleTitle>Immunomodulatory proteins FIP-gts and chloroquine induce caspase-independent cell death via autophagy for resensitizing cisplatin-resistant urothelial cancer cells.</ArticleTitle>
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<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Chloroquine, a lysosomal inhibitor, is used for malaria, rheumatoid arthritis, and lupus erythematosus therapy. In our previous study, FIP-gts, an immunomodulatory protein from Ganoderma tsugae, inhibited cell viability in lung cancer cells and urothelial cancer cells. Urothelial carcinoma is the most common type of bladder cancer. Cisplatin resistance is an important issue in urothelial carcinoma therapy.</AbstractText>
<AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">The aim of this study is to investigate the effect of combination treatment with FIP-gts and chloroquine on cytotoxicity to resensitize the cisplatin-resistant cells.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">FIP-gts and chloroquine cytotoxicity were determined by evaluating CCK-8 assay. Cell death pathways, ROS and cell cycle arrested were analysed through flow cytometry and Western blot. ShRNA targeting to autophagy-related genes were tested to evaluate their autophagic cell death for resistant urothelial cells.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">Using CCK-8 assay, chloroquine increased FIP-gts-induced cytotoxicity in parental and cisplatin-resistant urothelial cancer cell lines. On flow cytometry, chloroquine enhanced FIP-gts-mediated sub-G1 accumulation, annexin V positive signal and mitochondrial membrane potential loss. Caspase-3/PARP cascade and z-VAD-fmk were performed to prove that FIP-gts and chloroquine induced caspase-independent cell death. Using H2DCFDA staining and flow cytometry, FIP-gts and chloroquine did not induce ROS production. N-acetyl cysteine, a ROS scavenger, inhibited the cytotoxicity and LC3-II accumulation in FIP-gts and chloroquine-treated N/P cells. To elucidate the role of autophagy in caspase-independent cell death by FIP-gts and chloroquine, LC3 shRNA were used to inhibit autophagy in N/P cells. The capabilities of FIP-gts and chloroquine to induce cytotoxicity and sub-G1 phase accumulation were abolished in autophagy-defective cells. This is the first study to reveal the novel function of FIP-gts in triggering caspase-independent cell death in cisplatin-resistant urothelial cancer cells.</AbstractText>
<AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Chloroquine enhanced FIP-gts-induced autophagy dependent caspase-independent cell death via abundant autophagosome accumulation. Combination treatment with FIP-gts and chloroquine may provide a new strategy for urothelial cancer therapy.</AbstractText>
<CopyrightInformation>Copyright © 2016 Elsevier GmbH. All rights reserved.</CopyrightInformation>
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Data generation: Wed Mar 25 22:43:59 2020. Site generation: Sun Jan 31 12:44:45 2021