Pomiferin targets SERCA, mTOR, and P-gp to induce autophagic cell death in apoptosis-resistant cancer cells, and reverses the MDR phenotype in cisplatin-resistant tumors in vivo

Publication type:
Journal article
Metadata:
Autoren
  • Yuan-Qing Qu
  • Lin-Lin Song
  • Su-Wei Xu
  • Margaret Sum Yee Yu
  • Onat Kadioglu
  • Francesco Michelangeli
  • Betty Yuen Kwan Law
  • Thomas Efferth
  • Christopher Wai-Kei Lam
  • Vincent Kam Wai Wong
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000988645200001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phrs.2023.106769
eISSN
1096-1186
Externe Identifier
  • Clarivate Analytics Document Solution ID: G4CC3
  • PubMed Identifier: 37061145
ISSN
1043-6618
Zeitschrift
PHARMACOLOGICAL RESEARCH
Schlüsselwörter
  • Pomiferin
  • Chemoresistance
  • SERCA inhibitor
  • Autophagic cell death
  • P-gp inhibitor
  • Cisplatin-resistant
Artikelnummer
ARTN 106769
Datum der Veröffentlichung
2023
Status
Published
Titel
Pomiferin targets SERCA, mTOR, and P-gp to induce autophagic cell death in apoptosis-resistant cancer cells, and reverses the MDR phenotype in cisplatin-resistant tumors in vivo
Sub types
  • Article
Ausgabe der Zeitschrift
191

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Yuan-Qing Qu
  • Lin-Lin Song
  • Su-Wei Xu
  • Margaret Sum Yee Yu
  • Onat Kadioglu
  • Francesco Michelangeli
  • Betty Yuen Kwan Law
  • Thomas Efferth
  • Christopher Wai-Kei Lam
  • Vincent Kam Wai Wong
DOI
10.1016/j.phrs.2023.106769
ISSN
1043-6618
Zeitschrift
Pharmacological Research
Sprache
en
Artikelnummer
106769
Paginierung
106769 - 106769
Datum der Veröffentlichung
2023
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phrs.2023.106769
Datum der Datenerfassung
2023
Titel
Pomiferin targets SERCA, mTOR, and P-gp to induce autophagic cell death in apoptosis-resistant cancer cells, and reverses the MDR phenotype in cisplatin-resistant tumors in vivo
Ausgabe der Zeitschrift
191

Data source: Crossref

Abstract
Drug resistance in cancer has been classified as innate resistance or acquired resistance, which were characterized by apoptotic defects and ABC transporters overexpression respectively. Therefore, to preclude or reverse these resistance mechanisms could be a promising strategy to improve chemotherapeutic outcomes. In this study, a natural product from Osage Orange, pomiferin, was identified as a novel autophagy activator that circumvents innate resistance by triggering autophagic cell death via SERCA inhibition and activation of the CaMKKβ-AMPK-mTOR signaling cascade. In addition, pomiferin also directly inhibited the P-gp (MDR1/ABCB1) efflux and reversed acquired resistance by potentiating the accumulation and efficacy of the chemotherapeutic agent, cisplatin. In vivo study demonstrated that pomiferin triggered calcium-mediated tumor suppression and exhibited an anti-metastatic effect in the LLC-1 lung cancer-bearing mouse model. Moreover, as an adjuvant, pomiferin potentiated the anti-tumor effect of the chemotherapeutic agent, cisplatin, in RM-1 drug-resistant prostate cancer-bearing mouse model by specially attenuating ABCB1-mediated drug efflux, but not ABCC5, thereby promoting the accumulation of cisplatin in tumors. Collectively, pomiferin may serve as a novel effective agent for circumventing drug resistance in clinical applications.
Addresses
  • Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau; Faculty of Medicine, Macau University of Science and Technology, Macau.
Autoren
  • Yuan-Qing Qu
  • Lin-Lin Song
  • Su-Wei Xu
  • Margaret Sum Yee Yu
  • Onat Kadioglu
  • Francesco Michelangeli
  • Betty Yuen Kwan Law
  • Thomas Efferth
  • Christopher Wai-Kei Lam
  • Vincent Kam Wai Wong
DOI
10.1016/j.phrs.2023.106769
eISSN
1096-1186
Externe Identifier
  • PubMed Identifier: 37061145
Open access
false
ISSN
1043-6618
Zeitschrift
Pharmacological research
Schlüsselwörter
  • Cell Line, Tumor
  • Animals
  • Mice
  • Lung Neoplasms
  • Cisplatin
  • Antineoplastic Agents
  • Apoptosis
  • Drug Resistance, Neoplasm
  • Male
  • TOR Serine-Threonine Kinases
  • Autophagic Cell Death
Sprache
eng
Medium
Print-Electronic
Online publication date
2023
Paginierung
106769
Datum der Veröffentlichung
2023
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2023
Titel
Pomiferin targets SERCA, mTOR, and P-gp to induce autophagic cell death in apoptosis-resistant cancer cells, and reverses the MDR phenotype in cisplatin-resistant tumors in vivo.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
191

Data source: Europe PubMed Central

Abstract
Drug resistance in cancer has been classified as innate resistance or acquired resistance, which were characterized by apoptotic defects and ABC transporters overexpression respectively. Therefore, to preclude or reverse these resistance mechanisms could be a promising strategy to improve chemotherapeutic outcomes. In this study, a natural product from Osage Orange, pomiferin, was identified as a novel autophagy activator that circumvents innate resistance by triggering autophagic cell death via SERCA inhibition and activation of the CaMKKβ-AMPK-mTOR signaling cascade. In addition, pomiferin also directly inhibited the P-gp (MDR1/ABCB1) efflux and reversed acquired resistance by potentiating the accumulation and efficacy of the chemotherapeutic agent, cisplatin. In vivo study demonstrated that pomiferin triggered calcium-mediated tumor suppression and exhibited an anti-metastatic effect in the LLC-1 lung cancer-bearing mouse model. Moreover, as an adjuvant, pomiferin potentiated the anti-tumor effect of the chemotherapeutic agent, cisplatin, in RM-1 drug-resistant prostate cancer-bearing mouse model by specially attenuating ABCB1-mediated drug efflux, but not ABCC5, thereby promoting the accumulation of cisplatin in tumors. Collectively, pomiferin may serve as a novel effective agent for circumventing drug resistance in clinical applications.
Date of acceptance
2023
Autoren
  • Yuan-Qing Qu
  • Lin-Lin Song
  • Su-Wei Xu
  • Margaret Sum Yee Yu
  • Onat Kadioglu
  • Francesco Michelangeli
  • Betty Yuen Kwan Law
  • Thomas Efferth
  • Christopher Wai-Kei Lam
  • Vincent Kam Wai Wong
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/37061145
DOI
10.1016/j.phrs.2023.106769
eISSN
1096-1186
Zeitschrift
Pharmacol Res
Schlüsselwörter
  • Autophagic cell death
  • Chemoresistance
  • Cisplatin-resistant
  • P-gp inhibitor
  • Pomiferin
  • SERCA inhibitor
  • Male
  • Mice
  • Animals
  • Cisplatin
  • Antineoplastic Agents
  • Autophagic Cell Death
  • Drug Resistance, Neoplasm
  • Lung Neoplasms
  • Apoptosis
  • TOR Serine-Threonine Kinases
  • Cell Line, Tumor
Sprache
eng
Country
Netherlands
Paginierung
106769
PII
S1043-6618(23)00125-1
Datum der Veröffentlichung
2023
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Titel
Pomiferin targets SERCA, mTOR, and P-gp to induce autophagic cell death in apoptosis-resistant cancer cells, and reverses the MDR phenotype in cisplatin-resistant tumors in vivo.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
191

Data source: PubMed

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