Abstract 5255: Methionine restriction limits prostate tumor cell proliferation
Allott, EH; Tang, X; Masko, EM; Gaines, A; Abern, MR; Chi, J-TA; Freedland, SJ
Published in: Cancer Research
Introduction: Methionine restriction has been shown to have growth inhibitory effects in a number of tumor cell lines in vitro. Methionine restriction has previously been demonstrated to slow PC-3 prostate tumor cell growth in vivo, however not at dietary levels tolerable to humans. Up to 90% dietary methionine restriction has been demonstrated to be both tolerable and safe in a preliminary human clinical trial. We hypothesized that 80%-90% methionine restriction could limit prostate tumor cell growth in vitro and in vivo. Methods: We reduced methionine levels by 40%, 80%, 90% and 100% in prostate cancer cell lines in vitro, relative to standard RPMI medium. Cell proliferation and viability were measured using MTS and trypan blue assays, respectively. PC-3 cells were grafted into a xenograft nude mouse model and animals were randomized to standard chow, 80% or 90% methionine restricted diets. Plasma methionine levels were measured before and after the dietary intervention. Tumor volume was measured throughout the study and mice were sacrificed when tumors reached 1000 mm3. Results: Methionine restriction exerted a dose and time-dependent effect on PC-3 tumor cell proliferation and viability in vitro. Methionine restriction of 80% and 90% for a period of 6 days reduced PC-3 tumor cell line proliferation by 20% and 40%, respectively, as measured by MTS assay (p<0.0001). Following 6 days of 80% and 90% methionine restriction, PC-3 cell viability was reduced by 10% and 15%, respectively. We are currently awaiting results from our in vivo study which is underway. Discussion: Methionine restriction slows prostate tumor cell line growth and reduces cell line viability in vitro. Based upon these in vitro results we hypothesize that an 80% - 90% methionine restricted diet will slow tumor growth in vivo, and we await the results of this dietary intervention in mice. Methionine restriction at this clinically relevant level which is tolerable and safe to humans may have the potential to slow tumor growth in prostate cancer patients; however more preliminary studies are needed in order to establish whether 80%-90% methionine restriction actually does slow tumor growth in vivo and if so to understand the mechanisms by which this occurs.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5255. doi:1538-7445.AM2012-5255
