دورية أكاديمية
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Apaf1 nanoLuc biosensors identified lentinan as a potent synergizer of cisplatin in targeting hepatocellular carcinoma cells.

التفاصيل البيبلوغرافية
العنوان: Apaf1 nanoLuc biosensors identified lentinan as a potent synergizer of cisplatin in targeting hepatocellular carcinoma cells.
المؤلفون: Wang Z; Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, China., Qu K; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi 'an Jiaotong University, China., Zhou L; Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, China., Ren L; Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, China., Ren B; Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, China., Meng F; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi 'an Jiaotong University, China., Yu W; Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, China., Wang H; Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, China., Fan H; Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, China. Electronic address: hainingfan78@gmail.com.
المصدر: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2021 Nov 05; Vol. 577, pp. 45-51. Date of Electronic Publication: 2021 Aug 11.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
مواضيع طبية MeSH: Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Apoptotic Protease-Activating Factor 1/*metabolism , Biosensing Techniques/*methods , Carcinoma, Hepatocellular/*drug therapy , Liver Neoplasms/*drug therapy, Apoptosis/drug effects ; Apoptosis/genetics ; Apoptotic Protease-Activating Factor 1/genetics ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Cisplatin/administration & dosage ; Drug Synergism ; Hep G2 Cells ; Humans ; Lentinan/administration & dosage ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Mutation
مستخلص: Liver cancer is one of the most common malignancies that is difficult to treat due to late diagnosis and chemo-resistance. In the present study, we developed and validated a cell based split nanoLuc biosensor to monitor the Apaf1-Apaf1 interactions in response to apoptosis-inducing drugs such as cisplatin. We showed that the activity of split nanoLuc is reconstituted only in response to apoptotic inducer, cisplatin and in a dose-dependent manner. Apaf1 mutants which were unable to oligomerize failed to recover nanoLuc activity while constitutively active variant increased the nanoLuc activity. Generation of Apaf1 knockout HepG2 and treatment with cisplatin showed dramatic reduction in cell death suggesting that cisplatin mainly targets liver cancer cells through apoptosis. As the natural products are potent sources of compounds for adjuvant therapy, we screened a collection of natural products and identified lentinan as an inducer of apoptosome formation, a key step for induction of apoptosis. Lentinan is a polysaccharide with antitumor, pro-apoptotic properties that functions with poorly understood mechanisms. Lentinan was shown to have cytotoxic effects with the IC 50 of 650 μM. Sub-lethal lentinan concentration doubled the nanoLuc activity when co-treated with cisplatin. We also showed that lentinan hugely reduced the dose of cisplatin to induce certain amount of death and that lentinan co-treatment with cisplatin enhanced the Apaf1 transcription in HepG2 cells while lentinan or cisplatin alone failed to alter the transcription. In addition, lentinan and cisplatin co-treatment induced mitochondrial depolarization. This suggested that lentinan combinatorial therapy with cisplatin engaged a different signalling pathway to kill the liver cancer cells and that adjuvant therapy with lentinan can reduce the dose of cisplatin and thus reduce the possibility of chemo-resistance.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Apaf1; Chemo-resistance; Hepatocellular carcinoma; Lentinan; Split nanoLuc biosensors
المشرفين على المادة: 0 (APAF1 protein, human)
0 (Apoptotic Protease-Activating Factor 1)
37339-90-5 (Lentinan)
Q20Q21Q62J (Cisplatin)
تواريخ الأحداث: Date Created: 20210910 Date Completed: 20211126 Latest Revision: 20211126
رمز التحديث: 20231215
DOI: 10.1016/j.bbrc.2021.08.030
PMID: 34507064
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2104
DOI:10.1016/j.bbrc.2021.08.030