Methionine dependence of cancer and aging: methods and protocols
Cancer cells require exogenous methionine for survival and therefore methionine restriction is a promising
avenue for treatment. The basis for methionine dependence in cancer cells is still not entirely clear. While
the lack of the methionine salvage enzyme methylthioadenosine phosphorylase (MTAP) is associated with
methionine auxotrophy in cancer cells, there are other causes for tumors to require exogenous methionine.
Restricting methionine by diet or by enzyme depletion, alone or in combination with certain chemotherapeutics,
is a promising antitumor strategy.
The anti-cancer efficacy of methionine γ-lyase (MGL) from Clostridium sporogenes (C. sporogenes) is described. MGL was active against cancer cells in vitro and in vivo. Doxorubicin (DOX) and MGL were more effective on A549 human lung cancer growth inhibition than either agent alone in vitro and in vivo. The growth inhibitory effect of DOX + MGL on A549 xenograft in vivo was reflective of the results obtained in vitro.