Reproductive effects of a pegylated curcumin

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 34; no. 1; pp. 120 - 124
• Main Authors: Murphy, Caitlin J., Tang, Huadong, Van Kirk, Edward A., Shen, Youqing, Murdoch, William J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.08.2012; Elsevier
• Subjects: Accessory gland; Adenocarcinoma; Androgen Antagonists - chemistry; Androgen Antagonists - therapeutic use; Androgen Antagonists - toxicity; Animal models; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Antineoplastic Agents - toxicity; Antitumor agents; Biological and medical sciences; Cancer; Cell Line, Tumor; Curcuma longa; Curcumin; Curcumin - chemistry; Curcumin - therapeutic use; Curcumin - toxicity; Embryology: invertebrates and vertebrates. Teratology; Estrogens, Non-Steroidal - chemistry; Estrogens, Non-Steroidal - therapeutic use; Estrogens, Non-Steroidal - toxicity; Female; Fertility - drug effects; Fundamental and applied biological sciences. Psychology; Male; Mating; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Mouse; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Ovaries; Polyethylene glycol; Polyethylene Glycols - chemistry; Polyethylene Glycols - therapeutic use; Polyethylene Glycols - toxicity; Polyphenols; Puberty; Reproduction; Rhizomes; Side effects; Spermatogenesis; Spermatozoa - drug effects; Spermatozoa - physiology; Surfactants; Teratology. Teratogens; Testes; Testis - drug effects; Testis - metabolism; Testosterone; Testosterone - metabolism; Toxicology; Tumor Burden - drug effects; Tumors; Uterus - drug effects; Uterus - physiology; Vagina; Xenograft Model Antitumor Assays; Reproduction; Curcumin; Mouse; Polyethylene glycol; Cancer; Tyrosine kinase inhibitor; Rodentia; Malignant tumor; Ethylene oxide polymer; Vertebrata; Polyphenol; Mammalia; Animal; Phenols; Pegylated form
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2012.04.005

► A water-soluble conjugate of curcumin and polyethylene glycol with antitumor properties was constructed. ► Parenteral administration of pegylated curcumin affected reproductive functions in mice. ► Estrogenic, antiandrogenic, and antipregnancy effects were demonstrated. Curcumin, a polyphenol derived from the rhizome turmeric, has potential as an anticancer agent. We synthesized an amphipathic/surfactant pegylated curcumin (curcumin-PEG) designed for parenteral administration. Objectives of these investigations were to assess side-effects of a therapeutic regimen of curcumin-PEG in a preclinical model. Intraperitoneal (ip) tumor burdens were reduced in athymic female mice grafted with human SKOV-3 ovarian adenocarcinoma cells and injected intravenously (iv) with curcumin-PEG. There were no gross anatomical or histopathological effects detected in non-reproductive organs. Uteri (luminal fluid imbibition) and ovaries (decreased folliculogenesis) were affected by treatment. Curcumin-PEG ip hastened the onset of puberty in immature female mice. Live births were reduced in mature females housed with males and treated iv with curcumin-PEG; mating (vaginal plugs) was not affected. Accessory gland weights, testicular testosterone concentrations, and spermatogenesis were diminished in mature male mice following iv curcumin-PEG. Estrogenic/antiandrogenic and pregnancy-disrupting effects of a water soluble/bioavailable curcumin were demonstrated.