Protective effects of triterpene compounds against the cytotoxicity of cadmium in HepG2 cells.
The effects of triterpene compounds on cadmium toxicity were investigated in HepG2 cells. Ten triterpene compounds were examined, namely, betulin, soyasapogenol A, soyasapogenol B, ursolic acid, uvaol, oleanolic acid, friedelin, glycyrrhizin, 18alpha-glycyrrhetinic acid, and 18beta-glycyrrhetinic acid, and betulin, soyasapogenol A, and uvaol were found to reduce the toxicity of CdCl(2). In particular, betulin almost completely abolished the cytotoxicity of CdCl(2) at concentrations as low as 0. 1 microg/ml. The effects of betulin were particularly apparent when added to the culture medium before the addition of CdCl(2). Moreover, when HepG2 cells were incubated with betulin and then incubated in fresh betulin-free medium before the addition of CdCl(2), the toxic effects of cadmium were reduced. Betulin had no significant effect on the intracellular accumulation of cadmium, nor did it bind to cadmium, at least not in a test tube. When HepG2 cells were treated first with cycloheximide or actinomycin D, the subsequent protective effect of betulin against cadmium toxicity was significantly reduced, suggesting that betulin might protect cells against cadmium toxicity by inducing the synthesis of a certain protein or proteins. The synthesis of metallothionein, a protein that is known to reduce the toxicity of heavy metals, was not induced by betulin. However, using the differential display method, we confirmed that betulin promoted the expression of several genes. Our findings suggest that betulin might reduce cadmium toxicity by promoting the synthesis of certain proteins that protect cells against the toxic effects of cadmium.
Miura
N
N
Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Matsumoto
Y
Y
Miyairi
S
S
Nishiyama
S
S
Naganuma
A
A
D002104:Cadmium / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004336:Drug Antagonism; D006801:Humans; D020011:Protective Agents / Q000494:pharmacology*; D019685:Rosales / Q000737:chemistry; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000094062:Betulinic Acid
D002104:Cadmium; D020011:Protective Agents; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid