Vitamin E succinate suppresses prostate tumor growth by inducing apoptosis.
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.
Malafa
Mokenge P
MP
Division of GI Tumors, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. malafamp@moffitt.usf.edu
Fokum
Frida D
FD
Andoh
Jennifer
J
Neitzel
Leslie T
LT
Bandyopadhyay
Sucharita
S
Zhan
Rui
R
Iiizumi
Megumi
M
Furuta
Eiji
E
Horvath
Elizabeth
E
Watabe
Kounosuke
K
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
D014810:Vitamin E; C093516:CASP4 protein, human; D020169:Caspases; D053471:Caspases, Initiator; D024505:Tocopherols