PMID- 12409832
OWN - NLM
STAT- MEDLINE
DCOM- 20030123
LR  - 20190906
IS  - 1536-4828 (Electronic)
IS  - 0885-3177 (Linking)
VI  - 25
IP  - 4
DP  - 2002 Nov
TI  - Irsogladine malate up-regulates gap junctional intercellular communication 
      between pancreatic cancer cells via PKA pathway.
PG  - 373-7
AB  - INTRODUCTION: Gap junctions (GJs) are intercellular channels that aid 
      communication between coupling cells and may play a critical role in cell 
      differentiation and growth. Connexins (Cxs) are structural proteins of GJs. 
      Though several reports have demonstrated that Cx expression decreases in various 
      malignant tumors, a pancreatic cancer cell line, PANC-1, was reported to express 
      Cx43 mRNA. It is known that irsogladine malate (IM) can up-regulate gap 
      junctional intercellular communication (GJIC). We examined the effects of IM on 
      GJ between pancreatic cancer cells (PC cells) and the mechanism of GJ 
      up-regulation. METHODOLOGY: GJIC between PC cells (PANC-1) was evaluated by dye 
      transfer methods. The expression of Cx43 was estimated by Western blot analysis 
      with immunoprecipitation sample and immunohistochemical analysis. Intracellular 
      cAMP level was estimated by enzyme-linked immunoassay. RESULTS: IM increased cell 
      coupling in a dose-dependent manner (0M-10 ). Western blot analysis of Cx43 
      revealed that PANC-1 cells expressed Cx43 protein. Treatment with IM was found to 
      move localization of Cx43 immunoreactive spots from the cytoplasm to boundary 
      lesions with neighboring cells, but no major change was seen in the 
      phosphorylation state of Cx43. Intracellular cAMP level was increased by IM. The 
      PKA inhibitor H-89 and adenylyl cyclase inhibitor SQ22536 inhibited the effects 
      of IM. CONCLUSION: These results suggest that IM up-regulates GJIC between PC 
      cells via regulation of the PKA pathway. It also suggests a useful adjuvant of IM 
      to pancreatic cancer therapy.
FAU - Kawasaki, Yousuke
AU  - Kawasaki Y
AD  - First Department of Internal Medicine, Hiroshima University School of Medicine, 
      Hiroshima, Japan. ayanonyk@hiroshima-u.ac.jp
FAU - Tsuchida, Akira
AU  - Tsuchida A
FAU - Sasaki, Tamito
AU  - Sasaki T
FAU - Yamasaki, Souichirou
AU  - Yamasaki S
FAU - Kuwada, Yukio
AU  - Kuwada Y
FAU - Murakami, Masateru
AU  - Murakami M
FAU - Chayama, Kazuaki
AU  - Chayama K
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pancreas
JT  - Pancreas
JID - 8608542
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Connexin 43)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Triazines)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - QBX79NZC1D (irsogladine)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Biological Transport
MH  - Cell Communication
MH  - Cell Line
MH  - Connexin 43/metabolism
MH  - Cyclic AMP/analysis
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Dogs
MH  - Fluorescent Dyes/metabolism
MH  - Gap Junctions/*physiology
MH  - Pancreatic Neoplasms/*enzymology/metabolism/*physiopathology
MH  - Signal Transduction
MH  - Triazines/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
EDAT- 2002/11/01 04:00
MHDA- 2003/01/24 04:00
CRDT- 2002/11/01 04:00
PHST- 2002/11/01 04:00 [pubmed]
PHST- 2003/01/24 04:00 [medline]
PHST- 2002/11/01 04:00 [entrez]
AID - 00006676-200211000-00009 [pii]
AID - 10.1097/00006676-200211000-00009 [doi]
PST - ppublish
SO  - Pancreas. 2002 Nov;25(4):373-7. doi: 10.1097/00006676-200211000-00009.