Diethylstilbestrol Diphosphate

Diethylstilbestrol diphosphate induced direct cytotoxic effects in human androgen-insensitive prostate cancer cells DU145, 1-LN and PC-3 with LD50 values ranging from 19 to 25 micromolar. The growth inhibition was dependent on heat-labile phosphatases present in fetal calf serum, requiring conversion to diethylstilbestrol for cytotoxic activity. The cytotoxic effect was estrogen receptor-independent, as estrogen receptor-positive and -negative cells were equally responsive. Fluorescence microscopy with anti-tubulin and phalloidin staining showed no disruption of microtubule or actin filament architecture in PC-3 cells. Instead, diethylstilbestrol diphosphate treatment induced the formation of apoptotic bodies in nuclei, which was confirmed by DNA fragmentation analysis. Flow cytometry revealed an increase in hypodiploid apoptotic nuclei, depletion of G1- and S-phase cells, and accumulation of cells in G2/M phase in androgen-insensitive cells.

Fig. 1 Reduction of viability in PC-3 cells treated with diethylstilbestrol diphosphate. (Robertson C N.; et al. 1996)

Diethylstilbestrol diphosphate-derived nanoparticles were synthesized by conjugating diethylstilbestrol with phosphate, copper, indium and quantum dots, then labeled with technetium-99m for SPECT imaging of estrogen receptor-enriched cancers. The nanoparticles were evaluated in MCF-7 breast adenocarcinoma cells, PC-3 prostatic carcinoma cells and A-549 pulmonary epithelial cells for in vitro biological activity. In vivo lymph node imaging was performed in normal and receptor-blocked female New Zealand rabbits. Results showed that the 99mTc-labeled nanoparticles have potential for imaging estrogen receptor-enriched tumors including breast and prostate tumors and their metastases in the lung.

Fig. 2 Schema for DESCIP distribution in cancerous cells. (Moharrami P.; et al. 2017)