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
Iwagaki, H.; Fuchimoto, S.; Miyake, M.; Orita, K.
Gan to Kagaku Ryoho. Cancer and ChemoTherapy 15(9): 2725-2730
1988
ISSN/ISBN: 0385-0684 PMID: 2458072 Document Number: 320099
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.