PMID- 25013352
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211021
IS  - 1054-2523 (Print)
IS  - 1554-8120 (Electronic)
IS  - 1054-2523 (Linking)
VI  - 23
IP  - 8
DP  - 2014 Aug 1
TI  - Isothiocyanate analogs targeting CD44 receptor as an effective strategy against 
      colon cancer.
PG  - 3836-3851
AB  - Inflammatory pathway plays an important role in tumor cell progression of 
      colorectal cancers. Although colon cancer is considered as one of the leading 
      causes of death worldwide, very few drugs are available for its effective 
      treatment. Many studies have examined the effects of specific COX-2 and 5-LOX 
      inhibitors on human colorectal cancer, but the role of isothiocyanates (ITSCs) as 
      COX-LOX dual inhibitors engaged in hyaluronan-CD44 interaction has not been 
      studied. In the present work, we report series of ITSC analogs incorporating 
      bioisosteric thiosemicarbazone moiety. These inhibitors are effective against 
      panel of human colon cancer cell lines including COX-2 positive HCA-7, HT-29 
      cells lines, and hyaluronan synthase-2 (Has2) enzyme over-expressing transformed 
      intestinal epithelial Apc10.1Has2 cells. Specifically, our findings indicate that 
      HA-CD44v6-mediated COX-2/5-LOX signaling mediate survivin production, which in 
      turn, supports anti-apoptosis and chemo-resistance leading to colon cancer cell 
      survival. The over-expression of CD44v6shRNA as well as ITSC treatment 
      significantly decreases the survival of colon cancer cells. The present results 
      thus offer an opportunity to evolve potent inhibitors of HA synthesis and CD44v6 
      pathway and thus underscoring the importance of the ITSC analogs as 
      chemopreventive agents for targeting HA/CD44v6 pathway.
FAU - Misra, Suniti
AU  - Misra S
AD  - Regenerative Medicine and Cell Biology, Medical University of South Carolina, 
      Charleston, SC 29425, USA.
FAU - Ghatak, Shibnath
AU  - Ghatak S
AD  - Regenerative Medicine and Cell Biology, Medical University of South Carolina, 
      Charleston, SC 29425, USA.
FAU - Vyas, Alok
AU  - Vyas A
AD  - ISTRA, Department of Chemistry, Abeda Inamdar College, University of Pune, Pune 
      411001, India.
FAU - O'Brien, Paul
AU  - O'Brien P
AD  - Hematology/Oncology Division, Medical University of South Carolina, Charleston, 
      SC 29425, USA.
FAU - Markwald, Roger R
AU  - Markwald RR
AD  - Regenerative Medicine and Cell Biology, Medical University of South Carolina, 
      Charleston, SC 29425, USA.
FAU - Khetmalas, Madhukar
AU  - Khetmalas M
AD  - Department of Bioinformatics and Computer Science, Dr. D. Y. Patil Biotechnology 
      and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Tathawade, Pune 411033, 
      India.
FAU - Hascall, Vincent C
AU  - Hascall VC
AD  - Department of Biomedical Engineering/ND20, The Cleveland Clinic Foundation, 
      Cleveland, OH, USA.
FAU - McCarthy, James B
AU  - McCarthy JB
AD  - Department of Laboratory Medicine and Pathology, University of Minnesota Masonic 
      Cancer Center, Minneapolis, MN, USA.
FAU - Karamanos, Nikos K
AU  - Karamanos NK
AD  - Laboratory of Biochemistry, Department of Chemistry, University of Patras, 
      Patras, Greece.
FAU - Tammi, Markku I
AU  - Tammi MI
AD  - University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
FAU - Tammi, Raija H
AU  - Tammi RH
AD  - University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
FAU - Prestwitch, Glenn D
AU  - Prestwitch GD
AD  - Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT, USA.
FAU - Padhye, Subhash
AU  - Padhye S
AD  - ISTRA, Department of Chemistry, Abeda Inamdar College, University of Pune, Pune 
      411001, India.
LA  - eng
GR  - P30 AR050953/AR/NIAMS NIH HHS/United States
GR  - P20 GM103444/GM/NIGMS NIH HHS/United States
GR  - R01 HL033756/HL/NHLBI NIH HHS/United States
GR  - P30 GM103342/GM/NIGMS NIH HHS/United States
GR  - P20 RR016461/RR/NCRR NIH HHS/United States
GR  - P20 RR021949/RR/NCRR NIH HHS/United States
GR  - R03 CA167722/CA/NCI NIH HHS/United States
GR  - P20 RR016434/RR/NCRR NIH HHS/United States
GR  - P01 HL107147/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Med Chem Res
JT  - Medicinal chemistry research : an international journal for rapid communications 
      on design and mechanisms of action of biologically active agents
JID - 9211347
PMC - PMC4084864
MID - NIHMS572156
OTO - NOTNLM
OT  - Anti-cancer
OT  - CD44/hyaluronan
OT  - COX-LOX dual inhibition
OT  - Colon cancer
OT  - Isothiocyanate analogs
OT  - Molecular modeling
EDAT- 2014/07/12 06:00
MHDA- 2014/07/12 06:01
PMCR- 2015/08/01
CRDT- 2014/07/12 06:00
PHST- 2014/07/12 06:00 [entrez]
PHST- 2014/07/12 06:00 [pubmed]
PHST- 2014/07/12 06:01 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - 10.1007/s00044-014-0958-4 [doi]
PST - ppublish
SO  - Med Chem Res. 2014 Aug 1;23(8):3836-3851. doi: 10.1007/s00044-014-0958-4.