Fig. 1

Methionine dependency of cancer cells. a Methionine metabolism in mammals: the one carbon cycle is essential to regenerate methionine and S-adenosylmethionine (SAM). SAM is the major methyl donor in the cell and is involved in reactions for phospholipid synthesis, chromatin, RNA, and protein methylation, and one carbon donor pool homeostasis. b Illustration depicting the methionine dependency of cancer. Most cancer cells (red) do not grow in homocysteine growth medium (Met-Hcy+), whereas normal cells (blue) are unaffected. Green arrows indicate positive proliferation rates, red arrows indicate reduced or no proliferation. c MB468 and MB468res cells proliferate in methionine growth media (Met+) at similar rates. d But only the resistant cells (MB468res: R8, R21, R28) maintain proliferation in Met-Hcy+ media. Proliferation rates were quantified by luminescent cell viability assay. Error bars represent standard deviation. e Methionine stress resistant clone MB468res-R8 forms fewer colonies in soft agar than the parental MB468 cell line. Cells were plated in 0.3 % agar, cultured for 30 days, and stained with crystal violet. Colony values are the average of three independent experiments. Error bars indicate standard deviation