Prostate
carcinoma is a common
malignancy among males that results in high morbidity and mortality. Here, we have evaluated the capacity of
nucleoside analogue
BCH-4556 [
beta-L-(-)-dioxolane-cytidine] to control
prostate cancer progression in our syngeneic model of rat
prostate cancer using the rat
prostate cancer cell line Dunning R3227 Mat Ly Lu. Different concentrations (50 microM-1 mM) of
BCH-4556 resulted in a marked decrease and, eventually, a complete arrest of Mat Ly Lu cell growth in vitro. Cells were inoculated via intracardiac (i.c.) route into the left ventricle or by s.c. injection into the right flank of male Copenhagen rats. Following i.c. inoculation, experimental animals were treated with 75 mg/kg
BCH-4556 twice a day or with vehicle alone for 6 consecutive days, starting from day 1 or day 3 post-
tumor cell inoculation. Control and experimental animals were monitored for the development of
tumor metastases. Treatment with
BCH-4556 did not significantly change the development of skeletal
metastases and, hence, the time of development of hind limb
paralysis. Experimental animals, however, did show a marked reduction in the incidence and size of
tumor metastases at the adrenal glands. Following the development of palpable
tumors after s.c. injection of Mat Ly Lu cells on day 8 post
tumor cell inoculation, animals were treated i.p. with 25-75 mg/kg
BCH-4556 twice a day or with vehicle alone for 6 consecutive days. Control animals developed large primary
tumors and macroscopic
metastasis to lungs, lymph nodes, kidneys, and spleen. In contrast, experimental animals receiving
BCH-4556 showed a marked decrease in
tumor volume and
metastases after the last injection of
BCH-4556. The maximum dose of
BCH-4556 (75 mg/kg twice a day) caused a complete arrest in
tumor growth that was maintained for up to 4-6 days without any evidence of cytotoxicity. These antitumor effects of
BCH-4556 were more marked than those of
doxorubicin in blocking
tumor growth in this model of
prostate cancer, and it continued to be effective following three cycles of treatment, without manifesting any signs of drug resistance.