Thapsigargin Facts Sheet
This mini website about
thapsigargin was prepared by a student of BioInformatics, the Open University.
alternate names: thapsigargin
Thapsigargin, a plant-derived
sesquiterpene lactone (see above), is an extremely tight-binding inhibitor
of intracellular calcium (SERCA) pumps. We have shown that, in contrast to
its well known inhibition of the catalytic cycle as a whole, thapsigargin
binding actually activates phosphate-HOH oxygen exchange by enhancing the
hydrolysis of the E2P (see catalytic cycle). Thapsigargin greatly stabilises
the pump against denaturation in detergent, which suggests that it locks the
membrane helices together. This in turn suggests that the oxygen exchange
and accompanying domain movements in the head region of the protein are not
linked to full counter transport of protons, as previously hypothesised, but
rather may be associated with a single protonated form of the pump.\
Prostate cancer specific derivatives of thapsigargin
Although blocking SOCs offers one approach to depleting intracellular
calcium, this end-point can also be achieved through the use of thapsigargin
and its derivatives which target intracellular stores directly to induce
apoptosis in prostate cancer cells. Thapsigargin is not however selective to
the prostate and to avoid the risk of side-effects, Danish researchers in
collaboration with Johns Hopkins Oncology Center have developed a series of
inactive Thapsigargin prodrugs that can be activated by PSA. The prodrugs
thus synthesized demonstrated prostate cancer specificity suggesting that
they may represent novel therapeutic candidates for this disease..
Where to buy:
AGscientific: 10 mg = $290
LClabs: 10 mg =
the 10 selected thapsigargin abstracts
Effects of ionomycin and thapsigargin on ion
currents in oocytes of Bufo arenarum.
Biochemical characterization, distribution and
phylogenetic analysis of Drosophila melanogaster ryanodine and IP3
receptors, and thapsigargin-sensitive Ca2+ ATPase.
Histamine potentiates IP(3)-mediated Ca(2+)
release via thapsigargin-sensitive Ca(2+) pumps.
Bax plays a pivotal role in thapsigargin
-induced apoptosis of human colon cancer HCT116 cells by controlling Smac/Diablo
and Omi/HtrA2 release from mitochondria
The effects of nifedipine and
thapsigargin on the responses of pressurized rat mesenteric artery to
5-hydroxytryptamine and norepinephrine.
||The effect of
ursodeoxycholic acid on the survivin in thapsigargin-induced apoptosis.
||Role of protein tyrosine
phosphorylation in the thapsigargin-induced intracellular Ca(2+) store
depletion during human sperm acrosome reaction.
hormone insensitive, thapsigargin-sensitive Ca2+ store reduces basal
gonadotropin exocytosis and gene expression: comparison with
agonist-sensitive Ca2+ stores.
||Effects of thapsigargin on
stimulation frequency--dependent changes in mitochondrial calcium in rat
Thapsigargin blocks STP and LTP related calcium
enhancements in hippocampal CA1 area.
1. Wong, W.E. et al. (1993) Biochem. 289, 71-9
2. Low, A.M. et al. (1993) Eur. J. Pharmacol. 230, 53-62
3. Charlesworth, A. & Rozengurt, E. (1994) J. Biol. Chem. 269, 32528-35
4. Foskett, J.K. & Wong, D.C. (1994) J. Biol. Chem. 269, 31525-32
5. Furuya, Y. et al. (1994) Cancer Res. 54, 6167-75
6. Palmer, F.P. et al. (1994) Biochim. Biophys. Acta 1215, 190-7
Some effects of
- Potent, cell permeable IP3-independent intracellular
calcium releaser. Takemura, H. et al. J. Biol. Chem. 264:
- Inhibits microsomal Ca2+-ATPase. Thastrup, O. et al.
Agents Actions 27: 17-23 (1989).
- Rat mast cell histamine secretagogue. Patkar, S.A. Acta Pharm.
Suecica 15: 133-140 (1978). Agents Actions 9:
- Mouse skin tumor promoter with potency somewhat weaker than teleocidin
or PMA, but does not bind to protein kinase C or induce ornithine
decarboxylase activity. Hakii, H. et al. J. Cancer Res. Clin.
Oncol. 111: 177-181 (1986).
- Stimulates arachidonic acid metabolism in macrophages. Ohuchi, K.
et al. J. Cancer Res. Clin. Oncol. 113: 319-324 (1987).