Targeting the mitochondrial pathway to induce apoptosis/necrosis through ROS by a newly developed Schiff's base to overcome MDR in cancer

Publication type:
Journal article
Metadata:
Autoren
  • Soumya Basu
  • Avishek Ganguly
  • Paramita Chakraborty
  • Rupashree Sen
  • Kaushik Banerjee
  • Mitali Chatterjee
  • Thomas Efferth
  • Soumitra Kumar Choudhuri
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000300473200020&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.biochi.2011.10.004
eISSN
1638-6183
Externe Identifier
  • Clarivate Analytics Document Solution ID: 895CG
  • PubMed Identifier: 22037022
ISSN
0300-9084
Ausgabe der Veröffentlichung
1
Zeitschrift
BIOCHIMIE
Schlüsselwörter
  • Apoptosis/necrosis
  • Cancer multidrug resistance
  • Mitochondria
  • Potassium-N-(2-hydroxy-3-methoxy-benzaldehyde)-alaninate
  • (PHMBA)
  • Reactive oxygen species
Paginierung
166 - 183
Datum der Veröffentlichung
2012
Status
Published
Titel
Targeting the mitochondrial pathway to induce apoptosis/necrosis through ROS by a newly developed Schiff's base to overcome MDR in cancer
Sub types
  • Article
Ausgabe der Zeitschrift
94

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Soumya Basu
  • Avishek Ganguly
  • Paramita Chakraborty
  • Rupashree Sen
  • Kaushik Banerjee
  • Mitali Chatterjee
  • Thomas Efferth
  • Soumitra Kumar Choudhuri
DOI
10.1016/j.biochi.2011.10.004
ISSN
0300-9084
Ausgabe der Veröffentlichung
1
Zeitschrift
Biochimie
Sprache
en
Paginierung
166 - 183
Datum der Veröffentlichung
2012
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.biochi.2011.10.004
Datum der Datenerfassung
2021
Titel
Targeting the mitochondrial pathway to induce apoptosis/necrosis through ROS by a newly developed Schiff’s base to overcome MDR in cancer
Ausgabe der Zeitschrift
94

Data source: Crossref

Abstract
Multidrug resistance (MDR) in cancer, a major obstacle to successful application of cancer chemotherapy, is often characterized by over-expression of multidrug resistance-related proteins such as MRP1, P-gp or elevated glutathione (GSH) level. Efflux of drugs by functional P-gp, MRP1 and elevated GSH level can confer resistance to apoptosis induced by a range of different stimuli. Therefore, it is necessary to develop new cell death inducers with relatively lower toxicity toward non-malignant cells that can overcome MDR by induction of apoptotic or non-apoptotic cell death pathways. Herein we report the synthesis and spectroscopic characterization of a GSH depleting, redox active Schiff's base, viz., potassium-N-(2-hydroxy-3-methoxy-benzaldehyde)-alaninate (PHMBA). Cytotoxic potential of PHMBA has been studied in doxorubicin-resistant and -sensitive T lymphoblastic leukemia cells and Ehrlich ascites carcinoma (EAC) cells. PHMBA kills both the cell types irrespective of their drug-resistance phenotype following apoptotic/necrotic pathways. Moreover, PHMBA-induced cell death is associated with oxidative stress mediated mitochondrial pathway as the H(2)O(2) inhibitor PEG-Catalase abrogated PHMBA-induced apoptosis/necrosis. PHMBA induces anti-tumor activity in both doxorubicin-sensitive and -resistant EAC-tumor-bearing Swiss albino mice. The non-toxicity of PHMBA was also confirmed through cytotoxicity studies on normal cell lines like PBMC, NIH3T3 and Chang Liver. To summarise, our data provide compelling rationale for future clinical use of this redox active Schiff's base in treatment of cancer patients irrespective of their drug-resistance status.
Addresses
  • Department of In vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, India.
Autoren
  • Soumya Basu
  • Avishek Ganguly
  • Paramita Chakraborty
  • Rupashree Sen
  • Kaushik Banerjee
  • Mitali Chatterjee
  • Thomas Efferth
  • Thomas Efferth
  • Soumitra Kumar Choudhuri
DOI
10.1016/j.biochi.2011.10.004
eISSN
1638-6183
Externe Identifier
  • PubMed Identifier: 22037022
Funding acknowledgements
  • Indian Council of Medical Research: 5/13/53/2008/NCD-III
  • Indian Council of Medical Research: 3/2/2/200/2009/NCD-III
  • Indian Council of Medical Research: 5/13/18/2007/NCD-III
Open access
false
ISSN
0300-9084
Ausgabe der Veröffentlichung
1
Zeitschrift
Biochimie
Schlüsselwörter
  • Cell Line, Tumor
  • Mitochondria
  • Animals
  • Mice
  • Neoplasms
  • Necrosis
  • Calcium
  • Reactive Oxygen Species
  • Schiff Bases
  • Calpain
  • Glutathione
  • Flow Cytometry
  • Spectroscopy, Fourier Transform Infrared
  • Spectrophotometry, Ultraviolet
  • Magnetic Resonance Spectroscopy
  • Apoptosis
  • Drug Resistance, Neoplasm
  • Caspase 3
Sprache
eng
Medium
Print-Electronic
Online publication date
2011
Paginierung
166 - 183
Datum der Veröffentlichung
2012
Status
Published
Datum der Datenerfassung
2011
Titel
Targeting the mitochondrial pathway to induce apoptosis/necrosis through ROS by a newly developed Schiff's base to overcome MDR in cancer.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
94

Data source: Europe PubMed Central

Abstract
Multidrug resistance (MDR) in cancer, a major obstacle to successful application of cancer chemotherapy, is often characterized by over-expression of multidrug resistance-related proteins such as MRP1, P-gp or elevated glutathione (GSH) level. Efflux of drugs by functional P-gp, MRP1 and elevated GSH level can confer resistance to apoptosis induced by a range of different stimuli. Therefore, it is necessary to develop new cell death inducers with relatively lower toxicity toward non-malignant cells that can overcome MDR by induction of apoptotic or non-apoptotic cell death pathways. Herein we report the synthesis and spectroscopic characterization of a GSH depleting, redox active Schiff's base, viz., potassium-N-(2-hydroxy-3-methoxy-benzaldehyde)-alaninate (PHMBA). Cytotoxic potential of PHMBA has been studied in doxorubicin-resistant and -sensitive T lymphoblastic leukemia cells and Ehrlich ascites carcinoma (EAC) cells. PHMBA kills both the cell types irrespective of their drug-resistance phenotype following apoptotic/necrotic pathways. Moreover, PHMBA-induced cell death is associated with oxidative stress mediated mitochondrial pathway as the H(2)O(2) inhibitor PEG-Catalase abrogated PHMBA-induced apoptosis/necrosis. PHMBA induces anti-tumor activity in both doxorubicin-sensitive and -resistant EAC-tumor-bearing Swiss albino mice. The non-toxicity of PHMBA was also confirmed through cytotoxicity studies on normal cell lines like PBMC, NIH3T3 and Chang Liver. To summarise, our data provide compelling rationale for future clinical use of this redox active Schiff's base in treatment of cancer patients irrespective of their drug-resistance status.
Date of acceptance
2011
Autoren
  • Soumya Basu
  • Avishek Ganguly
  • Paramita Chakraborty
  • Rupashree Sen
  • Kaushik Banerjee
  • Mitali Chatterjee
  • Thomas Efferth
  • Soumitra Kumar Choudhuri
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/22037022
DOI
10.1016/j.biochi.2011.10.004
eISSN
1638-6183
Ausgabe der Veröffentlichung
1
Zeitschrift
Biochimie
Schlüsselwörter
  • Animals
  • Apoptosis
  • Calcium
  • Calpain
  • Caspase 3
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Flow Cytometry
  • Glutathione
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mitochondria
  • Necrosis
  • Neoplasms
  • Reactive Oxygen Species
  • Schiff Bases
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
Sprache
eng
Country
France
Paginierung
166 - 183
PII
S0300-9084(11)00383-X
Datum der Veröffentlichung
2012
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2012
Titel
Targeting the mitochondrial pathway to induce apoptosis/necrosis through ROS by a newly developed Schiff's base to overcome MDR in cancer.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
94

Data source: PubMed

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