Reproductive Effects of Pegylated Curcumin.

Curcumin, a phenolic extract from the rhizome turmeric, has potential (based largely on in vitro studies) as an anticancer agent. Unfortunately, bioavailability of curcumin in vivo is poor; absorption via the gastrointestinal tract is negligible and it is not readily miscible in aqueous injection vehicles. Recently we synthesized a water-soluble pegylated curcumin (curcumin-PEG) that when delivered intravenously (iv) exhibited antitumor activities (cell-cycle arrest/programmed death) in athymic mice grafted with human ovarian or breast cancer cells. The objectives of these investigations were to determine possible side-effects of curcumin-PEG on reproductive functions. Mature BALB/c strain female mice were housed with proven breeder males and received a daily injection (tail vein) of curcumin-PEG (0.5 mg) or phosphate-buffered saline (0.1 ml PBS control) over a period of twenty days (n = 21). There was no effect of curcumin-PEG on incidences of breeding (vaginal plugs). However, numbers of live births per dam were significantly reduced in the curcumin-PEG compared to control group. Onset of puberty, as assessed by time of vaginal opening, was significantly hastened in 15-day-old female mice treated (intraperitoneal injection) for five consecutive days with curcumin-PEG. Mature male mice were treated daily iv with curcumin-PEG (n = 10) or PBS (n = 8) for ten days. Accessory gland (seminal vesicle) weights were significantly reduced 48 h after the last injection of curcumin-PEG. These results indicate that curcumin-PEG can affect the reproductive systems of females and males. Experiments are underway to elucidate mechanisms of curcumin-PEG actions. Research supported by the National Institutes of Health (RR-016474) and Department of Defense Medical Research Program (BC-0083821). (poster)