[Monitoring of the effect of anticancer drugs on the membrane potential and cytoplasmic free calcium ion mobilization in cancer cells as a drug sensitivity test].
When the plasma membrane capacity to maintain an ionic gradient is correlated with the cell viability, the anticancer drug-induced-cation (K+, Ca2+) mobilization, an early event associated with cell death, might be used as a rapid in vitro drug sensitivity test. A cyanine dye, dis-C3-5, was used to determine the membrane potential (Em), which was calculated as the following formula; Em = -RT/F In ([K+] in/[K+] out) in cancer cell lines. The change in cytoplasmic free calcium ion ([Ca2+]i) mobilization induced by the drugs was measured by fluorescent dye Fura2-AM. The results suggest that the sensitive drug, which showed greater than or equal to 50% inhibition of succinate dehydrogenase activity in SDI test, induced greater than or equal to 30% fall of membrane potential after 2 hour exposure to the drugs and also induced [Ca2+]i mobilization. On the other hand, the resistant drug showed no change of Em and [Ca2+]i.
Iwagaki
H
H
1st Dept. of Surgery, Okayama University Medical School.
Fuchimoto
S
S
Miyake
M
M
Orita
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008564:Membrane Potentials; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007473:Ion Channels; D002118:Calcium