The effect of pH on biological activity of plant cytotoxin cauloside C.
The effect of plant carboxyl-containing glycoside cauloside C upon eucaryotic cells has been studied. The glycoside interacts with cells as a pH-dependent cytotoxin and increases K+ leakage and Ca2+ uptake with strong action in acidic media Cell viability after glycoside action at acidic pH may be recovered by the shift of medium pH from 5.6 to 7.4. Directed transport of low molecular weight effectors such as cAMP and Ca2+ to human embryo fibroblasts under the action of cauloside C has been demonstrated. Calcium uptake is accompanied by about a twofold stimulation of fibroblast proliferation in serum-free medium. The manifestation of the effect depends on the strictly determined time of the 'open' state of the membrane permeability (2 min) and upon concentration of glycoside in the medium (1 ng/ml) Cauloside C-stimulated Ca-transport is not blocked by Ca-channel blockers such as verapamil, diltiasem, and nitrendipine (all at a concentration of 1 x 10(-6) M) but these blockers inhibit cauloside C-stimulated proliferation of fibroblasts. We conclude that stimulation of fibroblast proliferation is caused by activation of membrane associated Ca-channels at the expense of calcium, incorporated into cells with cauloside C. The use of cauloside C as a new biochemical tool for cell permeabilisation is suggested.
Aminin
D L
DL
Pacific Institute of Bioorganic Chemistry, Far East Division of Russian Academy of Sciences, Russian Federation. aminin@piboc.marine.su
Agafonova
I G
IG
Gnedoi
S N
SN
Strigina
L I
LI
Anisimov
M M
MM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000493:pharmacokinetics; D002286:Carcinoma, Ehrlich Tumor; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D003603:Cytotoxins / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006027:Glycosides / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009447:Neuroblastoma; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011188:Potassium / Q000493:pharmacokinetics; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D003603:Cytotoxins; D006027:Glycosides; D014316:Tritium; D009828:Oleanolic Acid; C018245:cauloside C; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium