Abstract B36: Methionine modulates p53 and induces cell cycle arrest G1 in breast and prostate cancer cell lines

After being treated with methionine, the cell cycle progression of breast and prostate cancer cells were evaluated by flow cytometry. The following results were obtained:

There is a clear cell cycle arrest at G1 phase in breast and prostate cancer cells, showing a specific characteristic: MCF-7 (breast cancer cells) and LNCaP (prostate cancer cells) which contain wild-type p53 show arrest at G1 phase. MCF-7 cells are more sensitive to methionine, there are more MCF-7 cells than LNCaP cells that were arrested in G1 phase. However, DU-145 cells, which contain mutated p53, were arrested at S phase.

For comparison, we evaluated the effects of methionine on cell cycle progression of MCF-10A (immortal non-tumorigenic human breast epithelial cells) and BPH-1 (normal human prostate cells). Interestingly, treating of MCF-10A and BPH-1 cells with the same dose of methionine caused no changes in cell cycle progression as compared to those cells without being treated with methionine.

We also investigated the effects of methionine on several colon-derived cell lines. Treating of LS174 containing wild p53, SW480 containing mutated p53 and NCM460 (normal colon cell) with methionine caused no modifications in cell cycle progression as compared those without being treated with methionine.

The effects of methionine on the apoptotic rate of all above-mentioned cells were determined. The percentage of apoptotic cells of all these cells after being treated with methionine is less than 3%, suggesting that there is no significant effect of methionine on apoptosis in both normal and cancer cells.

These observations indicate that: a) methionine has a clear predisposition with breast and prostate cancer cell lines that contain a wild p53; b) its effects are selective only for breast and prostate but not for colon-derived cells and c) it only causes a clear cell cycle arrest in G1 and no apoptotic mechanism is involved

Therefore, we reasoned that in addition to acting via its modulation of p53 as indicated by our previous results , there may be other mechanism (s) involved in its effects on cell cycle progression. Its effects on hormone-sensitive breast and prostate cancer cells but not on hormone-sensitive colon cells suggest that a hormone-dependent pathway may be involved. Further work is needed to fully explore this potential pathway.