| First Author | Petersen NH | Year | 2013 |
| Journal | Cancer Cell | Volume | 24 |
| Issue | 3 | Pages | 379-93 |
| PubMed ID | 24029234 | Mgi Jnum | J:202602 |
| Mgi Id | MGI:5520106 | Doi | 10.1016/j.ccr.2013.08.003 |
| Citation | Petersen NH, et al. (2013) Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase. Cancer Cell 24(3):379-93 |
| abstractText | Lysosomal membrane permeabilization and subsequent cell death may prove useful in cancer treatment, provided that cancer cell lysosomes can be specifically targeted. Here, we identify acid sphingomyelinase (ASM) inhibition as a selective means to destabilize cancer cell lysosomes. Lysosome-destabilizing experimental anticancer agent siramesine inhibits ASM by interfering with the binding of ASM to its essential lysosomal cofactor, bis(monoacylglycero)phosphate. Like siramesine, several clinically relevant ASM inhibitors trigger cancer-specific lysosomal cell death, reduce tumor growth in vivo, and revert multidrug resistance. Their cancer selectivity is associated with transformation-associated reduction in ASM expression and subsequent failure to maintain sphingomyelin hydrolysis during drug exposure. Taken together, these data identify ASM as an attractive target for cancer therapy. |
