BACKGROUNDEtoposide‐induced apoptosis in prostate carcinoma cells is associated with changes in the elemental content of the cells. The authors previously reported that calcitonin and bombesin inhibited etoposide‐induced apoptosis in these cells. In the current study, the authors investigated whether these neuropeptides block the etoposide‐induced changes in elemental content.METHODSCells from the PC‐3 and Du 145 prostate carcinoma cell lines were grown either on solid substrates or on thin plastic films on titanium electron microscopy grids, and they were exposed to etoposide for 48 hours in the absence or presence of calcitonin and bombesin. After the exposure, the cells were frozen and freeze dried, and their elemental content was analyzed by energy‐dispersive X‐ray microanalysis in both in the scanning electron microscope and the scanning transmission electron microscope.RESULTSEtoposide treatment consistently induced an increase in the cellular Na concentration and a decrease in the cellular K concentration, resulting in a marked increase of the Na/K ratio and also an increase in the phosphorus:sulphur (P/S) ratio. Both bombesin and calcitonin inhibited the etoposide‐induced changes in the cellular Na/K ratio, and calcitonin, but not bombesin, inhibited the changes in the P/S ratio. No significant elemental changes were found with bombesin or calcitonin alone.CONCLUSIONSThe neuropeptides bombesin and calcitonin, which inhibited etoposide‐induced apoptosis, also inhibited the etoposide‐induced elemental changes in prostate carcinoma cells. This important fact strengthens the link between apoptosis and changes in the intracellular elemental content. This correlation provides an objective basis for the study of neuropeptide target points and may be helpful for alternative therapeutic protocols using neuropeptide inhibitors in the treatment of patients with advanced prostatic carcinoma. Cancer 2002;94:368–77. © 2002 American Cancer Society.