title: Methaneseleninic acid and γ-Tocopherol combination inhibits prostate tumor growth in Vivo in a xenograft mouse model.
abstract: Studies have shown that vitamin E and selenium possess antiproliferative effects against prostate cancer (PCa). However, results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) suggest that vitamin E (α-tocopheryl acetate; 400 mg) and/or selenium (L-selenomethionine; 200 μg) were ineffective against PCa in humans. It is arguable that the selected dose/formulation of vitamin E/selenium were not optimal in SELECT. Thus, additional studies are needed to define the appropriate formulations/dose regimens of these agents. Here, we investigated the effect of methaneseleninic acid (MSA; 41 µg/kg) and/or γ-tocopherol (γT; 20.8 mg/kg or 41.7 mg/kg) in Nu/J mice implanted with 22Rν1 tumors. MSA (41 µg/kg) and γT (20.8 mg/kg) combination was most consistent in imparting anti-proliferative response; resulting in a significant decrease in i) tumor volume/weight, ii) serum PSA, and iii) Ki-67 immunostaining. Further, we observed i) an upregulation of pro-apoptosis Bax and a down-regulation of the pro-survival Bcl2, and ii) an increase in pro-apoptosis Bad. Furthermore, the combination resulted in a modulation of apolipoprotein E, selenoprotein P and Nrf2 in a fashion that favors antiproliferative responses. Overall, our study suggested that a combination of MSA and γT, at lower dose regimen, could be useful in PCa management.
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, WI.
authors.forename: Chandra K
authors.initials: CK
authors.lastname: Singh
authors.forename: Mary A
authors.initials: MA
authors.lastname: Ndiaye
authors.forename: Imtiaz A
authors.initials: IA
authors.lastname: Siddiqui
authors.forename: Minakshi
authors.initials: M
authors.lastname: Nihal
authors.forename: Thomas
authors.initials: T
authors.lastname: Havighurst
authors.forename: KyungMann
authors.initials: K
authors.lastname: Kim
authors.forename: Weixiong
authors.initials: W
authors.lastname: Zhong
authors.forename: Hasan
authors.initials: H
authors.lastname: Mukhtar
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, WI; University of Wisconsin Carbone Cancer Center, Madison, WI.
authors.forename: Nihal
authors.initials: N
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016566:Organoselenium Compounds / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D024504:gamma-Tocopherol / Q000008:administration & dosage
chemical_list: D016566:Organoselenium Compounds; D024504:gamma-Tocopherol; C008493:methylselenic acid