PMID- 25358602
OWN - NLM
STAT- MEDLINE
DCOM- 20160122
LR  - 20240109
IS  - 1098-2744 (Electronic)
IS  - 0899-1987 (Linking)
VI  - 54
IP  - 12
DP  - 2015 Dec
TI  - Low fucose containing bacterial polysaccharide facilitate mitochondria-dependent 
      ROS-induced apoptosis of human lung epithelial carcinoma via controlled 
      regulation of MAPKs-mediated Nrf2/Keap1 homeostasis signaling.
PG  - 1636-55
LID - 10.1002/mc.22236 [doi]
AB  - Reactive oxygen species (ROS), the key mediators of cellular oxidative stress and 
      redox dysregulation involved in cancer initiation and progression, have recently 
      emerged as promising targets for anticancer drug discovery. Continuous free 
      radical assault upsets homeostasis in cellular redox system and regulates the 
      associated signaling pathways to mediate stress-induced cell death. This study 
      investigates the dose-specific pro-oxidative behavior of a bacterial fucose 
      polysaccharide, which attenuated proliferation of different cancer cells. In the 
      fermentation process, Bacillus megaterium RB-05 [GenBank Accession Number 
      HM371417] was found to biosynthesize a polysaccharide with low-fucose content 
      (4.9%), which conferred the maximum anti-proliferative activity (750 microg/mL) 
      against human lung cancer epithelial cells (A549) during preliminary screening. 
      Structural elucidation and morphological characterization of the duly purified 
      polysaccharide was done using HPLC, GC-MS, (1)H/(13)C NMR, and microscopy. The 
      polysaccharide exhibited concentration- and time-dependent anti-proliferative 
      effects against A549 cells by inducing intracellular ROS level and regulating the 
      mitochondrial membrane-permeability following the apoptotic pathway. This process 
      encompasses activation of caspase-8/9/3/7, increase in the ratio of Bax/Bcl2 
      ratio, translocation of Bcl2-associated X protein (Bax) and cytochrome c, 
      decrease in expression of anti-apoptotic members of Bcl2 family, and 
      phosphorylation of mitogen activated protein kinases (MAPKs). Apoptosis was 
      attenuated upon pretreatment with specific caspase-inhibitors. Simultaneously, 
      during apoptosis, the ROS-mediated stress as well as activated MAPKs triggered 
      nuclear translocation of transcription factors like nuclear factor 
      (erythroid-derived)-like 2 (Nrf2) and promoted further transcription of 
      downstream cytoprotective genes, which somehow perturbed the chemotherapeutic 
      efficacy of the polysaccharide, although using CuPP, a chemical inhibitor of 
      HO-1, apoptosis increased significantly (P < 0.05).
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Chowdhury, Sougata Roy
AU  - Chowdhury SR
AD  - Materials Science Centre, Indian Institute of Technology Kharagpur, Kharagpur, 
      WB, India.
AD  - Department of Zoology, Immunology Lab, University of Calcutta, Kolkata, WB, 
      India.
FAU - Sengupta, Suman
AU  - Sengupta S
AD  - Department of Zoology, Immunology Lab, University of Calcutta, Kolkata, WB, 
      India.
FAU - Biswas, Subir
AU  - Biswas S
AD  - Department of Zoology, Immunology Lab, University of Calcutta, Kolkata, WB, 
      India.
FAU - Sen, Ramkrishna
AU  - Sen R
AD  - Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, 
      WB, India.
FAU - Sinha, Tridib Kumar
AU  - Sinha TK
AD  - Materials Science Centre, Indian Institute of Technology Kharagpur, Kharagpur, 
      WB, India.
FAU - Basak, Ratan Kumar
AU  - Basak RK
AD  - Materials Science Centre, Indian Institute of Technology Kharagpur, Kharagpur, 
      WB, India.
FAU - Adhikari, Basudam
AU  - Adhikari B
AD  - Materials Science Centre, Indian Institute of Technology Kharagpur, Kharagpur, 
      WB, India.
FAU - Bhattacharyya, Arindam
AU  - Bhattacharyya A
AD  - Department of Zoology, Immunology Lab, University of Calcutta, Kolkata, WB, 
      India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141030
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (KEAP1 protein, human)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Polysaccharides, Bacterial)
RN  - 0 (Reactive Oxygen Species)
RN  - 28RYY2IV3F (Fucose)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Carcinoma/metabolism
MH  - Cell Line, Tumor
MH  - Epithelial Cells/metabolism
MH  - Fucose/pharmacology
MH  - HeLa Cells
MH  - Homeostasis/drug effects
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Kelch-Like ECH-Associated Protein 1
MH  - Lung Neoplasms/*metabolism
MH  - MCF-7 Cells
MH  - Mitochondria/*drug effects/metabolism
MH  - Mitogen-Activated Protein Kinase Kinases/*metabolism
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Polysaccharides, Bacterial/*pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - ROS
OT  - apoptosis
OT  - cell signaling
OT  - fucose polysaccharide
OT  - lung carcinoma
EDAT- 2014/11/02 06:00
MHDA- 2016/01/23 06:00
CRDT- 2014/11/01 06:00
PHST- 2014/03/17 00:00 [received]
PHST- 2014/08/19 00:00 [revised]
PHST- 2014/09/11 00:00 [accepted]
PHST- 2014/11/01 06:00 [entrez]
PHST- 2014/11/02 06:00 [pubmed]
PHST- 2016/01/23 06:00 [medline]
AID - 10.1002/mc.22236 [doi]
PST - ppublish
SO  - Mol Carcinog. 2015 Dec;54(12):1636-55. doi: 10.1002/mc.22236. Epub 2014 Oct 30.