Abstract 2679: Color-coded selective chemotherapy of methioninase-synchronized S-phase cancer cells expressing cell-cycle-specific fluorescent reporters: A general approach to the treatment of cancer

Abstract

Abstract Cancer cells of all types have a generally elevated requirement for methionine compared to normal cells. This phenomenon is termed methionine-dependence and may be due to excessive methylation reactions in cancer cells, since methionine is the global source of cellular methyl groups. Deprivation of methionine α,β lyase (methioninase or METase) selectively arrests cancer cells during late S-phase, where they are highly sensitive to chemotherapy drugs which damage DNA. Cancer cells, transformed to express different color fluorescent reporters during specific phases of the cell cycle (fluorescent ubiquitination-based cell cycle indicator [FUCCI]), were used to monitor the onset of the S-phase block due to methionine deprivation effected by METase. The S-phase-blocked cancer cells fluoresced yellow or green, in contrast to cancer cells in G1 which fluoresced red. Cancer cells, synchronously blocked in S-phase by METase and identified by their yellow-green fluorescence, were administered chemotherapy drugs which interact with DNA or block DNA synthesis such as doxorubicin, cisplatin or 5-fluorouracil. We have termed this strategy color-coded chemotherapy. The procedure was highly effective against the cancer cells. In contrast, treatment of cancer cells with drugs only, and without methioninase-effected S-phase synchrony, led to the majority of the cancer cell population being blocked in G phase (red fluorescent) where they were resistant to the drugs. The selective anticancer strategy and technology described in this report, whereby cancer cells are selectively and synchronously blocked in S-phase in the most drug-sensitive phase of the cell cycle where they are identified by fluorescent reporters and then treated with S-phase-specific-drugs, should be a general approach to the treatment of cancer. 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 2679. doi:1538-7445.AM2012-2679