Abstract:
Depriving cells of arginine, a semi-essential amino acid, is a developing strategy to target various cancer types. However, little is known about the effect of arginine-degrading enzymes in breast cancer, a disease of diverse molecular and phenotypic subtypes. In this project, we utilized a pharmacologically formulated human recombinant arginase (HuArgI(Co)-PEG5000) to evaluate the impact of arginine deprivation on breast cancer. We studied three breast cancer cell lines MCF-7 (a non-metastatic model for luminal breast cancer), UACC-2087 (a slow-growing model of triple negative breast cancer), and MDA-MB-231 (a highly aggressive and metastatic model of triple negative breast cancer). Using wound healing assay, Ki67 immunofluorescence assay, and annexin v pi assay, we respectively found that a 72-hour HuArgI(Co)-PEG5000 treatment mitigated MCF-7 and UACC-2087 cells’ migration, proliferation and survival. Interestingly, while treatment of MDA-MB-231 for a shorter time frame (24h) with HuArgI(Co)-PEG5000 did not result in robust anti-migratory or anti-proliferative effects, longer (72h) incubations induced a level of cell death in this cell line superseding that of UACC-2087 and MDA-MB-231. Our findings suggest the presence of differential mechanisms of action for arginine depriving enzymes across breast cancer subtypes, and point towards robust cytotoxic effects in highly proliferative triple negative breast cancer cells.
