PMID- 29567572
OWN - NLM
STAT- MEDLINE
DCOM- 20180917
LR  - 20180917
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 154
DP  - 2018 May 30
TI  - Unveiling anticancer potential of glibenclamide: Its synergistic cytotoxicity 
      with doxorubicin on cancer cells.
PG  - 294-301
LID - S0731-7085(17)32944-8 [pii]
LID - 10.1016/j.jpba.2018.03.025 [doi]
AB  - Drug repurposing has been an emerging therapeutic strategy, which involves 
      exploration of a new therapeutic approach for the use of an existing drug. 
      Glibenclamide (Gli) is an anti-diabetic sulfonylurea drug extensively used for 
      the treatment of type-2 diabetes, it has also been shown to possess 
      anti-proliferative effect against several types of tumors. The present study was 
      executed to understand the mechanisms underlying the interaction of Gli with DNA 
      under physiological conditions. The binding mechanism of Gli with DNA was 
      scrutinized by UV-vis absorption spectroscopy and fluorescence emission 
      spectroscopy. The conformational changes and electrochemical properties were 
      analyzed by circular dichroism spectroscopy and cyclic voltammetry. Isothermal 
      titration calorimetry was employed to examine the thermodynamic changes and 
      molecular docking technique used to analyze the interaction mode of Gli with DNA. 
      The spectroscopic studies revealed that Gli interacts with DNA through groove 
      binding mode. Further, isothermal titration calorimetry depicted a stronger mode 
      of interaction favorably groove-binding. Recently, systemic combination therapy 
      has shown significant promise in inhibiting multiple targets simultaneously 
      yielding high therapeutic competence with lesser side effects. With this concern, 
      we intended to study the combined cytotoxicity of Gli with doxorubicin (Dox). The 
      results of MTT assay and acridine orange (AO)/ethidium bromide (EtBr) staining 
      showed synergistic cytotoxicity of Gli + Dox combination on HepG2 & A549 cells. 
      The present study documents the intricate mechanism of Gli-DNA interaction and 
      delivers a multifaceted access for chemotherapy by Gli + Dox combination.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Subramaniyam, Nithyananthan
AU  - Subramaniyam N
AD  - Department of Biochemistry and Molecular Biology, Pondicherry University, 
      Puducherry 605 014, India.
FAU - Arumugam, Suyavaran
AU  - Arumugam S
AD  - Department of Biochemistry and Molecular Biology, Pondicherry University, 
      Puducherry 605 014, India.
FAU - Ezthupurakkal, Preedia Babu
AU  - Ezthupurakkal PB
AD  - Department of Biochemistry and Molecular Biology, Pondicherry University, 
      Puducherry 605 014, India.
FAU - Ariraman, Subastri
AU  - Ariraman S
AD  - Department of Biochemistry and Molecular Biology, Pondicherry University, 
      Puducherry 605 014, India.
FAU - Biswas, Indrani
AU  - Biswas I
AD  - Department of Biochemistry and Molecular Biology, Pondicherry University, 
      Puducherry 605 014, India.
FAU - Muthuvel, Suresh Kumar
AU  - Muthuvel SK
AD  - Centre for Bioinformatics, Pondicherry University, Puducherry 605 014, India.
FAU - Balakrishnan, Aristatile
AU  - Balakrishnan A
AD  - Department of Food Science and Nutrition, College of Food and Agricultural 
      Science, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia.
FAU - Alshammari, Ghedeir M
AU  - Alshammari GM
AD  - Department of Food Science and Nutrition, College of Food and Agricultural 
      Science, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia.
FAU - Chinnasamy, Thirunavukkarasu
AU  - Chinnasamy T
AD  - Department of Biochemistry and Molecular Biology, Pondicherry University, 
      Puducherry 605 014, India. Electronic address: tarasu.bbm@pondiuni.edu.in.
LA  - eng
PT  - Journal Article
DEP - 20180314
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cytotoxins)
RN  - 80168379AG (Doxorubicin)
RN  - 9007-49-2 (DNA)
RN  - SX6K58TVWC (Glyburide)
SB  - IM
MH  - A549 Cells
MH  - Antineoplastic Agents/*pharmacology
MH  - Calorimetry/methods
MH  - Cell Line, Tumor
MH  - Circular Dichroism/methods
MH  - Cytotoxins/*pharmacology
MH  - DNA/drug effects
MH  - Doxorubicin/*pharmacology
MH  - Drug Synergism
MH  - Fluorescence
MH  - Glyburide/*pharmacology
MH  - Hep G2 Cells
MH  - Humans
MH  - Molecular Docking Simulation/methods
MH  - Spectrometry, Fluorescence/methods
MH  - Thermodynamics
OTO - NOTNLM
OT  - Anti-cancer
OT  - Combination therapy
OT  - DNA interaction
OT  - Glibenclamide
OT  - Grove binding
EDAT- 2018/03/24 06:00
MHDA- 2018/09/18 06:00
CRDT- 2018/03/24 06:00
PHST- 2017/11/30 00:00 [received]
PHST- 2018/03/12 00:00 [revised]
PHST- 2018/03/13 00:00 [accepted]
PHST- 2018/03/24 06:00 [pubmed]
PHST- 2018/09/18 06:00 [medline]
PHST- 2018/03/24 06:00 [entrez]
AID - S0731-7085(17)32944-8 [pii]
AID - 10.1016/j.jpba.2018.03.025 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2018 May 30;154:294-301. doi: 10.1016/j.jpba.2018.03.025. 
      Epub 2018 Mar 14.