title: 2-methoxyestradiol Prevents LNCaP Tumor Development in Nude Mice: Potential Role of G2/M Regulatory Proteins.
abstract: Nontoxic naturally occurring metabolite of estrogen namely 2-methoxyestradial (2ME2) found in serum and urine has been shown to be antitumorigenic in various tumor models including the prostate. A recent study conducted in breast cancer cells showed growth stimulatory effect of 2ME2 when used at low concentrations (10-750 nM). Studies from our laboratory has demonstrated prostate tumor preventive ability of 50 mg/kg 2-ME2. In this study we show that concentrations of 2-ME2 as low as 1 µM is sufficient to inhibit proliferation and induce apoptosis in androgen responsive LNCaP cells. In addition oral administration of doses lower than 50 mg/kg prevented prostate tumor development in LNCaP xenograft model. The observed tumor growth inhibition was associated with induction of apoptosis, increased expression of Wee1 kinase and p34cdc2. In addition administration of 25 mg/kg 2-ME2 prevented tumor development significantly that is associated with reduction in serum PSA levels.
authors.affiliation: Department of Urology, School of Medicine, 7703 Floyd Curl Drive, University of Texas Health Science Center, San Antonio, TX 78229.
authors.forename: Cara
authors.initials: C
authors.lastname: Horny
authors.affiliation: Department of Urology, School of Medicine, 7703 Floyd Curl Drive, University of Texas Health Science Center, San Antonio, TX 78229.
authors.forename: Muralimanoharan Sri
authors.initials: MS
authors.lastname: Balasubashini
authors.affiliation: Department of Urology, School of Medicine, 7703 Floyd Curl Drive, University of Texas Health Science Center, San Antonio, TX 78229.
authors.forename: Krishna
authors.initials: K
authors.lastname: Komanduri
authors.affiliation: Department of Urology, School of Medicine, 7703 Floyd Curl Drive, University of Texas Health Science Center, San Antonio, TX 78229.
authors.forename: Manonmani
authors.initials: M
authors.lastname: Ganapathy
authors.affiliation: Department of Urology, School of Medicine, 7703 Floyd Curl Drive, University of Texas Health Science Center, San Antonio, TX 78229.
authors.forename: I-Tien
authors.initials: IT
authors.lastname: Yeh
authors.affiliation: Department of Urology, School of Medicine, 7703 Floyd Curl Drive, University of Texas Health Science Center, San Antonio, TX 78229.
authors.forename: Rita
authors.initials: R
authors.lastname: Ghosh
authors.affiliation: Department of Urology, School of Medicine, 7703 Floyd Curl Drive, University of Texas Health Science Center, San Antonio, TX 78229.
authors.forename: Addanki P
authors.initials: AP
authors.lastname: Kumar
keywords: 2-methoxyestradiol; PSA; apoptosis; prostate cancer prevention