Supplementary Figure S1 from NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment

Dong, Tiange; Dave, Priyal; Yoo, EunJeong; Ebright, Brandon; Ahluwalia, Kabir; Zhou, Eugene; Asante, Isaac; Salimova, Malika; Pei, Hua; Lin, Tracey; Mead, Andrew; Li, Zeyang; Humayun, Mark; Petasis, Nicos A.; Epstein, Alan L.; Louie, Stan G.

doi:10.1158/1535-7163.22522777.v1

15357163mct210414-sup-265300_2_supp_7358525_qzjt3d.docx (17.92 MB)

Supplementary Figure S1 from NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment

journal contribution

posted on 2023-04-03, 18:46 authored by Tiange Dong, Priyal Dave, EunJeong Yoo, Brandon Ebright, Kabir Ahluwalia, Eugene Zhou, Isaac Asante, Malika Salimova, Hua Pei, Tracey Lin, Andrew Mead, Zeyang Li, Mark Humayun, Nicos A. Petasis, Alan L. Epstein, Stan G. Louie

Figure S1 shows the gating strategy for PMN apoptosis analysis, RT-PCR, immunofluorescence staining, and flow cytometry analyses of FPR2/ALX-transfected HEK cells, effect of NAP1051 on dTHP-1 cells with selective kinase inhibitors, and Western blot with normal HEK cells and FPR2/ALX-transfected HEK cells

History

ARTICLE ABSTRACT

Resolving tumor-associated inflammation in the tumor microenvironment (TME) may promote antitumor effects. Lipoxin A4 (LXA4) is a short-lived endogenous bioactive lipid with potent anti-inflammatory and pro-resolving properties. Here, a biomimetic of LXA4, NAP1051, was shown to have LXA4-like in vitro properties and antitumor activity in colorectal cancer xenograft models. NAP1051 inhibited neutrophil chemotaxis toward fMLP and dose-dependently promoted dTHP-1 efferocytosis which was equipotent to aspirin-triggered lipoxin A4 (ATLA). In dTHP-1 cells, NAP1051 induced strong phosphorylation on ERK1/2 and AKT similar to formyl peptide receptor 2 (FPR2/ALX) agonists. In two mouse xenograft colorectal cancer models, NAP1051 significantly inhibited tumor growth when given orally at 4.8 to 5 mg/kg/day. Flow cytometric analyses showed that NAP1051 reduced splenic and intratumoral neutrophil and myeloid-derived suppressor cell populations, which correlated to the antitumor effect. In addition, NAP1051 reduced NETosis in the TME while stimulating T-cell recruitment. Overall, these results show that NAP1051 possesses key lipoxin-like properties and has antitumor activity against colorectal cancer via modulation of neutrophils and NETosis in the TME.