New strategy in cancel therapy with reference tomethionine-depletion

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Methionine (Met) is an important supplier of methyl radicals which will methylate double strand of DNA after replication to protect from DNA digestion by endonuclease. The present study was investigated the new strategy in anticancer therapy in reference to the higher Met-dependency of malignant tumor cells comparing with normal cells. When human culture tumor cells were assessed using Met- and/or homocysteine-depleting medium, 7 of 9 (78%) strains were Met-dependent. Thirteen human tumor xenografts in nude mice were treated with Met-depleting diet, and 4 of 13 (31%) strains were found to be Met-dependent. The Met-dependency was observed in a various kind of tumors, suggesting a wide antitumor spectrum of Met-depleting therapy for clinical cancer. In addition, some modulating antitumor activity of Met-depleting therapy was observed in combination with cisplatin and 5-fluorouracil. The antitumor activity of cisplatin was significantly enhanced by the Met-depleting therapy on Met-independent human breast carcinoma xenograft, MX-1. Met-depleting therapy increased the thymidylate synthetase inhibition by 5-fluorouracil in Met-partly dependent human gastric cancer, SC-1-NU.Met-depleting therapy elucidated antitumor activity on Met-dependent tumors in vitro and in vivo, and modulated the antitumor activity of cisplatin and 5-fluorouracil even on Met-independent or -partial dependent tumors. Met-depleting therapy is promising for further investigation for clinical human tumors.