Abstract P4-07-04: Methioninase cell-cycle synchronization potentiates chemotherapy for breast cancer

Abstract

Abstract Deprivation of methionine selectively arrests cancer cells during late S-phase (Proc. Natl. Acad. Sci. USA 77, 7306–7310, 1980; Biochim. Biophys. Acta, Reviews on Cancer 738, 49–87, 1984), where they are highly sensitive to chemotherapy drugs which damage DNA (J. Natl. Cancer Inst. 76, 629–639, 1986). Cancer cells, transformed to express different color fluorescent reporters during specific phases of the cell cycle (Cell 132, 487–498, 2008), were used to monitor the onset of the S/G2-phase block due to methionine deprivation effected by recombinant methioninase (rMETase). The S/G2-phase blocked cancer cells fluoresced yellow or green in contrast to cancer cells in G1 which fluoresced red. Cancer cells, including MCF-7 breast cancer, synchronously blocked in S/G2-phase by rMETase, were identified by their yellow-green fluorescence and allowed to accumulate to the maximum extent. At the point of maximum yellow/green cells in the culture, the cells were administered chemotherapy drugs which interact with DNA or block DNA synthesis such as doxorubicin. We termed this procedure color-coded chemotherapy (CCC). CCC was highly effective against the cancer cells (90% cell kill). In contrast, treatment of cancer cells with drugs only, and without rMETase-effected S/G2-phase synchrony, led to the majority of the cancer cell population being blocked in G1 phase (red fluorescent) where they were resistant to the drugs (40% cell kill). CCC, which identifies, by fluorescent color, when cancer cells are blocked in S/G2-phase by a unique cell-cycle-blocking agent, rMETase, demonstrates the potential of cell-synchronization-based chemotherapy for breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-07-04.