Calcium restriction inhibits cancer cell proliferation in vitro

Abstract

Prostate and breast cancer cells metastasize to the bone. Strontium‐89 (Sr‐89) is a radioisotope that is used for treating bone metastases. The effect of strontium on calcium uptake was studied in human fetal osteoblast (hFOB) as well as androgen independent PC‐3 human prostate and MDA‐MB231 human breast cancer cells using digitized fluorescence microscopy in cells preloaded with Fura‐2AM. The effect of calcium deprivation on cell growth was studied using the MTT assay. When compared to cultures grown in complete medium, calcium and serum deprivation for 24 hours decreased cell growth by 80, 58 and 52 percent in hFOB, MDA‐MB231 and PC‐3 cells respectively. Addition of strontium chloride (up to 2 mM) did not cause further growth inhibition in calcium and serum starved medium. Calcium deprivation caused a G1 block and decreased the proportion of cells in the S phase. PC‐3 cells cultured for 24 hours in complete calcium containing medium supplemented with fetal bovine serum had a cell cycle distribution of 56% G1, 18.4% G2 and 25.6% S phase cells. These parameters shifted to 74.5% G1, 12.8% G2 and 12.6 % S phase cells in calcium and serum starved medium. Although strontium did not affect cell growth, it inhibited uptake of calcium by PC‐3 and MDA‐MB231 cells. Uptake of calcium from the medium by cells was inhibited by the anti diarrhea drug loperamide, which is a calcium channel blocker. Interestingly, loperamide inhibited hFOB and MDA‐MB231 cell growth even in complete medium. Preferential inhibition of calcium uptake by cancer cells may be an option in cancer therapy.(Supported in part by USMRMC grants DAMD17‐03‐1‐0759, DAMD17‐03‐1‐0123, 2 G12 RR003048 from RCMI, NCRR, NIH and R 25HL003679 from HLBI, NIH)