Intracellular accumulation of free calcium in mouse tumor cells exposed to anticancer drugs.
Alterations in concentrations of intracellular free calcium ([Ca2+]i) were examined in mouse sarcoma S-180 cells exposed to cisplatin, mitomycin C and adriamycin, as related to cell viability. The [Ca2+]i was measured using the fluorescent Ca2+ indicator, fura-2. During the first 24 hr of incubation of the cells in vitro, in the presence of the drugs, the [Ca2+]i was lower than in the control cells. After 24 hr of incubation, the [Ca2+]i began to increase at a time when the cell viability was reduced to 50% of the controls, and finally exceeded 1 microM with reduction to 10%. The increase in [Ca2+]i was reciprocal to the loss of the cell viability. Changes in Ca2+ concentrations in the medium did not alter the results. These findings suggest that in the presence of anticancer drugs there is an accumulation of free Ca2+ with a release of this ion from internal stores and that cell death follows disruption in the homeostasis of intracellular Ca2+.
Kohnoe
S
S
Cancer Center, Kyushu University Hospital, Fukuoka, Japan.
Maehara
Y
Y
Emi
Y
Y
Takahashi
I
I
Yoshida
M
M
Sugimachi
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D016257:Fura-2; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016685:Mitomycin / Q000494:pharmacology; D012510:Sarcoma 180 / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016685:Mitomycin; D004317:Doxorubicin; D002945:Cisplatin; D002118:Calcium; D016257:Fura-2