Exploring the role of S-Adenosyl Methionine Decarboxylase (AMD1) in the growth, migration, metabolism and drug-combination profile of non-small cell lung cancer cells

Non-small cell lung cancer (NSCLC) accounts for 85% of and is associated with the poorest prognosis survival. Current chemotherapy against NSCLC limited to traditional chemotherapy, a high incidence adverse effects. Polyamines (putrescine, spermidine spermine) are small polycationic alkylamines increased in patients non-small (NSCLC). essential growth almost every type cell. Polyamine synthesis regulated by activity ornithine decarboxylase (ODC) S-Adenosylmethionine (AMD1) enzymes. Whereas ODC has been extensively studied, little known about role AMD1 metabolism cells. ADM1 catabolizes decarboxylated-S-adenosyl methionine, which, turn, acts as an aminopropyl donor spermine synthesis. Thus, inhibition would impair polyamine metabolism, affecting proliferation. In this work, we studied We used two lines (H1299 A549 cells). First, identified immunoblotting. Then, attempt delete protein using CRISPR-Cas9 system. Also, SAM486A, pharmacologic inhibitor AMD1, explore effect on through untargeted GC-MS metabolomics. evaluated migration viability cells exposed SAM486A transwell resazurin reduction methods, respectively. Finally, assessed synergistic other inhibitors such eflornithine (an inhibitor) MDL 72527 (a non-selective oxidase). When comparing H1299 lines, found that significantly greater levels protein. choose AMD1. got partial deletion CRISPR, but was enough decrease proliferation significantly. also decreased concentration-dependent manner both lines. As expected, SAM486 induced significant accumulation putrescine, despite not decreasing levels. when combined inhibitors, 72527, suggesting parallel rate-limiting enzymes more efficient reducing These results indicate could be interesting target explored look combinatory strategies polyamines or vivo. Funding: ANID-FONDECYT #1201378 No conflict interest.