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

摘要

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 lmol (6.65 mg/kg body weight) of Ca 37 significantly inhibited the growth of the prostate xenografted tumors, whereas 6 lmol (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.