PMID- 12842827
OWN - NLM
STAT- MEDLINE
DCOM- 20031202
LR  - 20211203
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 285
IP  - 5
DP  - 2003 Nov
TI  - 5,6-Dichloro-ribifuranosylbenzimidazole- and apigenin-induced sensitization of 
      colon cancer cells to TNF-alpha-mediated apoptosis.
PG  - G919-28
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine involved in 
      the expression of many genes integral to the inflammatory response. In addition, 
      it activates both apoptotic and survival pathways, the latter being mediated 
      through the activation of the transcription factor nuclear factor-kappaB 
      (NF-kappaB). Protein kinase CK2, a serine-threonine kinase that is universally 
      upregulated in human malignancies, may be involved at multiple levels in this 
      process. However, its role in mediating a survival response within colon cancer 
      cells remains incompletely understood. Here we report that inhibition of CK2 in 
      HCT-116 and HT-29 cells with the use of two specific CK2 inhibitors, 
      5,6-dichloro-ribifuranosylbenzimidazole (DRB) and apigenin, effected a 
      synergistic reduction in cell survival when used in conjunction with TNF-alpha. 
      Furthermore, there was a demonstrable synergistic reduction in colony formation 
      in soft agar with the use of the same combinations. Western blot analysis showed 
      that poly-ADP ribose polymerase and procaspase-3 cleavage complemented the 
      fluorescence-activated cell sorter analysis findings of significantly increased 
      subdiploid DNA-containing cell populations using these conditions. Remarkably, 
      these events occurred in the absence of any reduction in the expression of the 
      Bcl-2 family members Bcl-2, Mcl-1, and Bcl-xL or any change in the proapoptotic 
      molecules Bad or Bax. One-hybrid NF-kappaB promoter assays utilizing a Gal4-p65 
      transactivation domain construct revealed that the TNF-induced transactivation 
      was inhibited by both DRB and apigenin. This was associated with a concomitant 
      reduction in the expression of a recognized anti-apoptotic NF-kappaB target, 
      manganese superoxide dismutase, demonstrated by Q-PCR. Our findings indicate a 
      potentially novel strategy for the treatment of colon cancer, one that targets 
      CK2 simultaneous with TNF-alpha administration.
FAU - Farah, Myriam
AU  - Farah M
AD  - Division of Gastroenterology, Univ. of British Columbia, 100-2647 Willow St., 
      Vancouver BC V5Z 3P1, Canada.
FAU - Parhar, Kuljit
AU  - Parhar K
FAU - Moussavi, Maryam
AU  - Moussavi M
FAU - Eivemark, Sharlene
AU  - Eivemark S
FAU - Salh, Baljinder
AU  - Salh B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030703
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 53-85-0 (Dichlororibofuranosylbenzimidazole)
RN  - 7V515PI7F6 (Apigenin)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apigenin
MH  - *Apoptosis
MH  - Casein Kinase II
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Colonic Neoplasms/pathology/*physiopathology
MH  - Dichlororibofuranosylbenzimidazole/*pharmacology
MH  - Diploidy
MH  - Drug Synergism
MH  - Enzyme Inhibitors/*pharmacology
MH  - Flavonoids/*pharmacology
MH  - HCT116 Cells
MH  - Humans
MH  - I-kappa B Kinase
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/genetics
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Superoxide Dismutase/metabolism
MH  - Transcriptional Activation/drug effects
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
EDAT- 2003/07/05 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/07/05 05:00
PHST- 2003/07/05 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/07/05 05:00 [entrez]
AID - 00205.2003 [pii]
AID - 10.1152/ajpgi.00205.2003 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2003 Nov;285(5):G919-28. doi: 
      10.1152/ajpgi.00205.2003. Epub 2003 Jul 3.