PMID- 8253522
OWN - NLM
STAT- MEDLINE
DCOM- 19940110
LR  - 20190708
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 55
IP  - 6
DP  - 1993 Dec 2
TI  - Ability of the non-phorbol ester-type tumor-promoter thapsigargin to mimic the 
      stimulatory effects of 12-0-tetradecanoylphorbol-13-acetate on ornithine 
      decarboxylase activity, hydroperoxide production, and macromolecule synthesis in 
      mouse epidermis in vivo.
PG  - 1036-43
AB  - The biochemical effects of the non-12-0-tetradecanoylphorbol-13-acetate 
      (TPA)-type tumor promoter thapsigargin (TG), which does not bind to the 
      phorbol-ester receptor, or activate protein kinase C (PKC) or increase inositol 
      polyphosphates, were characterized in mouse epidermis in vivo. The cold scraping 
      method is required to detect the induction of ornithine decarboxylase (ODC) 
      activity by TG, a response much smaller than that caused by TPA and with a 
      different time course. TG pre-treatments do not alter or cause a refractory state 
      against ODC induction by TPA. But TG stimulates hydroperoxide (HPx) production 
      and RNA, protein, and DNA synthesis almost as much as TPA. Moreover, the 
      sequential effects of TG and TPA on DNA synthesis are identical: early inhibition 
      at 8 hr followed by maximal stimulation at 16-32 hr. TG-stimulated HPx production 
      requires protein synthesis and xanthine oxidase, phospholipase A2, and 
      lipoxygenase activities but not RNA and DNA synthesis, and cyclooxygenase and 
      protease activities. The HPx response to TG is not mimicked by the PKC activator 
      prostratin or inhibited by pre-treatments with prostratin or specific PKC 
      inhibitors. However, the Ca(2+)-ATPase inhibitor cyclopiazonic acid and the Ca2+ 
      ionophore and weak ODC inducer A23187 mimic remarkably the HPx responses to TG 
      and TPA. Since TG and A23187 are known to be, respectively, weak and incomplete 
      tumor promoters as compared with TPA, the present results suggest that the HPx 
      responses common to Ca(2+)-mobilizing and TPA- or non-TPA-type agents are 
      insufficient to achieve tumor promotion in the absence of major ODC induction.
FAU - Perchellet, E M
AU  - Perchellet EM
AD  - Anti-Cancer Drug Laboratory, Kansas State University, Manhattan 66506-4901.
FAU - Gali, H U
AU  - Gali HU
FAU - Gao, X M
AU  - Gao XM
FAU - Perchellet, J P
AU  - Perchellet JP
LA  - eng
GR  - CA56662/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Carcinogens)
RN  - 0 (Terpenes)
RN  - 67526-95-8 (Thapsigargin)
RN  - 9007-49-2 (DNA)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.17.3.2 (Xanthine Oxidase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 4.1.1.17 (Ornithine Decarboxylase)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Animals
MH  - Carcinogens/*pharmacology
MH  - DNA/biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Induction
MH  - Female
MH  - Hydrogen Peroxide/*metabolism
MH  - Mice
MH  - Ornithine Decarboxylase/*biosynthesis
MH  - Protein Kinase C/metabolism
MH  - Skin/drug effects/*metabolism
MH  - Terpenes/*pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Thapsigargin
MH  - Xanthine Oxidase/metabolism
EDAT- 1993/12/02 00:00
MHDA- 1993/12/02 00:01
CRDT- 1993/12/02 00:00
PHST- 1993/12/02 00:00 [pubmed]
PHST- 1993/12/02 00:01 [medline]
PHST- 1993/12/02 00:00 [entrez]
AID - 10.1002/ijc.2910550626 [doi]
PST - ppublish
SO  - Int J Cancer. 1993 Dec 2;55(6):1036-43. doi: 10.1002/ijc.2910550626.