Effect of extracellular cations on the chemotherapeutic efficacy of anticancer drugs

Abstract

Cancer development and the efficiency of chemotherapy relies on the patients calcium-related pathological status such as hyper- or hypocalcernia. In the present study, we investigated the effect of extracellular cations such as calcium and magnesium on the therapeutic efficacy of antitumor drugs. The analytic parameters used were cellular drug uptake/excretion and the chemosensitivity of the human breast cancer cell lines, MCF7 and MCF7/ADR. Both calcium and magnesium ions decreased the membrane permeability of cancer cells, which was determined by cell size analysis. These divalent ions also lowered the drug uptake and the cytoplasmic levels of rhodamine 123 and adriamycin, suggesting that they might interfere with the diffusion of these drugs by modifying the physical properties of the cytoplasmic membrane. The acute cytotoxicity of adriamycin after a short period of incubation correlated with changes in its cytoplasmic level. Our results indicate that these extracellular cations might play an important rale in the therapeutic activties of anticancer drugs in cancer patients. These results also provide insight a new aspect of chemotherapy, because they suggest that the therapeutic doses of anti-cancer drugs should be modified in cancer-bearing patients presenting with abnormal blood calcium levels.