A monocarbonyl analogue of curcumin, 1,5-bis(3-hydroxyphenyl)-1,4- pentadiene-3-one (Ca 37), exhibits potent growth suppressive activity and enhances the inhibitory effect of curcumin on human prostate cancer cells

Prostate carcinoma is one of the leading causes of cancer-related morbidity and mortality in males in western countries. Curcumin exhibits growth-suppressive activity against several cancers, including prostate cancer, but it has poor bioavailability. The purpose of this study was to evaluate the anticancer potency and mechanism of a curcumin analogue, 1,5-bis(3- hydroxyphenyl)-1,4-pentadiene-3-one (Ca 37), in human prostate cancer. Studies were performed in established human prostate cancer cell lines (PC-3 and DU145) as well as in a murine xenograft tumor (PC-3) model. Ca 37 presented a preferential suppression capacity against growth and migration toward prostate cancer cells compared with curcumin. Ca 37 impaired the bioenergetics system, promoted cell cycle arrest and apoptosis activation in PC-3 cells. In addition, 0.5 μmol (6.65 mg/kg body weight) of Ca 37 significantly inhibited the growth of the prostate xenografted tumors, whereas 6 μmol (110 mg/kg body weight) of curcumin had little effect. Furthermore, a combination of Ca 37 and curcumin resulted in enhanced antitumor activity in prostate cancer cells. N-Acetylcysteine abrogated both reactive oxygen species (ROS) production and viability loss induced by Ca 37 but partially prevented growth inhibition in PC-3 cells treated with curcumin alone, or a combination with Ca 37. The data indicate that induction of ROS plays a vital role in the growth inhibitory effect of Ca 37 in PC-3 cells. This study suggests that Ca 37, alone or in combination with curcumin, may be a promising anticancer agent for prostate cancer therapy.