TY - JOUR
T1 - Daptomycin suppresses tumor migration and angiogenesis via binding to ribosomal protein S19 in humans
AU - Cho, Sung Min
AU - Lee, Hwa Jung
AU - Karuso, Peter
AU - Kwon, Ho Jeong
PY - 2021/10
Y1 - 2021/10
N2 - We have previously reported that daptomycin (DAP), a last resort antibiotic, binds to ribosomal protein S19 (RPS19) in humans and exhibits selective anti-cancer activity against MCF7 breast cancer cells. Here, we investigated the role of RPS19 in the anti-cancer effects of DAP and have found that DAP does not induce autophagy, apoptosis or cell viability but does reduce cell proliferation. Our results suggest that an extraribosomal function of RPS19 involves the regulation of vascular endothelial growth factor (VEGF) but not EGF, PDGF or FGF. Engagement of RPS19 by DAP was shown by CETSA and ITDRFCETSA assays, and knocking down of RPS19 with siRNA increased the potency of DAP in MCF7 cells. In addition, DAP suppressed the secretion of VEGF in cancer cells and thereby inhibited cell migration. Collectively, these data provide an outline of the underlying mechanism of how DAP exhibits anti-cancer activity and suggests that RPS19 could be a promising target for the development of new anticancer drugs.
AB - We have previously reported that daptomycin (DAP), a last resort antibiotic, binds to ribosomal protein S19 (RPS19) in humans and exhibits selective anti-cancer activity against MCF7 breast cancer cells. Here, we investigated the role of RPS19 in the anti-cancer effects of DAP and have found that DAP does not induce autophagy, apoptosis or cell viability but does reduce cell proliferation. Our results suggest that an extraribosomal function of RPS19 involves the regulation of vascular endothelial growth factor (VEGF) but not EGF, PDGF or FGF. Engagement of RPS19 by DAP was shown by CETSA and ITDRFCETSA assays, and knocking down of RPS19 with siRNA increased the potency of DAP in MCF7 cells. In addition, DAP suppressed the secretion of VEGF in cancer cells and thereby inhibited cell migration. Collectively, these data provide an outline of the underlying mechanism of how DAP exhibits anti-cancer activity and suggests that RPS19 could be a promising target for the development of new anticancer drugs.
UR - http://www.scopus.com/inward/record.url?scp=85110550592&partnerID=8YFLogxK
U2 - 10.1038/s41429-021-00446-x
DO - 10.1038/s41429-021-00446-x
M3 - Article
C2 - 34253886
AN - SCOPUS:85110550592
SN - 0021-8820
VL - 74
SP - 726
EP - 733
JO - Journal of Antibiotics
JF - Journal of Antibiotics
IS - 10
ER -