title: Vitamin E succinate suppresses prostate tumor growth by inducing apoptosis.
abstract: Prostate cancer is a major cause of cancer death and morbidity in western countries. However, because of its intrinsic nature of chemoresistance, there is only limited systemic therapy available for the patients. Vitamin E (VE) has been under intensive study as a chemopreventive agent for various types of cancers. Preclinical studies suggest that vitamin E succinate (VES) is the most effective antitumor analogue of VE, yet there are scarce studies of VES in prostate cancer. In this study, we investigated the effects of VES on a panel of prostate cancer cells, and a xenograft model of prostate cancer. Our results indicate that VES significantly inhibited proliferation and induced apoptosis of prostate cancer cell lines in a dose and time dependent manner. The results of microarray analysis followed by real-time RT-PCR and inhibitor analyses indicated that the VES-induced apoptosis is mediated by caspase-4 in prostate tumor cells. In our animal model of prostate cancer in SCID mouse, daily injection of VES significantly suppressed tumor growth as well as lung metastases. These results suggest a potential therapeutic utility of VES for patients with prostate cancer.
authors.affiliation: Division of GI Tumors, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. malafamp@moffitt.usf.edu
authors.forename: Mokenge P
authors.initials: MP
authors.lastname: Malafa
authors.forename: Frida D
authors.initials: FD
authors.lastname: Fokum
authors.forename: Jennifer
authors.initials: J
authors.lastname: Andoh
authors.forename: Leslie T
authors.initials: LT
authors.lastname: Neitzel
authors.forename: Sucharita
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Rui
authors.initials: R
authors.lastname: Zhan
authors.forename: Megumi
authors.initials: M
authors.lastname: Iiizumi
authors.forename: Eiji
authors.initials: E
authors.lastname: Furuta
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Horvath
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Watabe
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000096:biosynthesis / Q000378:metabolism; D053471:Caspases, Initiator; D049109:Cell Proliferation / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000473:pathology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024505:Tocopherols; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014810:Vitamin E; C093516:CASP4 protein, human; D020169:Caspases; D053471:Caspases, Initiator; D024505:Tocopherols