Abstract 601: Momordicine-I treatment reduces the triple negative breast cancer growth and alters the M2 phenotype of macrophages in tumor microenvironment

Abstract Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with a worse prognosis. The goal of this study is to examine whether Momordicine-I (M-I), a key bioactive compound from Momordica charantia, displays an anti-cancer activity and the potential mechanism. We treated human and mouse TNBC cell lines, MDA-MB-231 and 4T1, with M-I in a dose-dependent manner for 48 hr. We observed a significant inhibition of cell growth. To understand the potential mechanism, we treated these cells with vehicle or M-I and cell lysates were prepared after 48 hr. We found that M-I inhibited pSTAT3, cyclinD1 and c-Myc expression in M-I treated cells. We next evaluated the anti-tumor efficacy of M-I in orthotopic breast cancer mouse model. MDA-MB-231 cells were implanted into the mammary fat pad of nude mice. Tumor bearing (∼80 mm3 in volume) mice were divided into two groups. One group received M-I (30 mg/kg/day) and the other group received vehicle as a control. Tumor volumes were significantly reduced in the M-I treated group compared to the control group. Our previous study showed that M-I treatment alters macrophage phenotype in a different cancer model. We next examined the status of tumor associated macrophages (TAMs) in TNBC tumors. TAMs are mainly considered M2-like macrophages, which plays a crucial role in mediating the interaction between tumor cells and the immune cells. To examine the specific TAM polarization in vivo, RNA from control and treated tumors was analyzed for macrophage polarization using specific primers. Since nude mice contain macrophages, we examined the status of Arg1 and IRF-4 (M2 marker) from the tumor treated with vehicle or M-I. We found a significant reduction in treated tumors. We also performed an in vitro experiment where conditioned media of 4T1 cells with or without M-I treatment were incubated with immortalized bone marrow derived mouse macrophages (iMac) cells and examined the expression of several macrophage markers. We observed that M-I treatment significantly reduced M2 phenotype of iMac cells. Co-culture experiment with or without M-I treated MDA-MB-231 cells with PMA treated THP-1 displayed downregulation of Arg1 and IL-10 expression. Our data demonstrates that M-I has potential as a candidate for TNBC therapy and inhibits the M2 polarization of macrophages. Further work is underway using 4T1 mouse model to understand M-I mediated tumor growth inhibition. Citation Format: Ruchi A. Patel, Ellen T. Tran, Kousik Kesh, Ratna B. Ray. Momordicine-I treatment reduces the triple negative breast cancer growth and alters the M2 phenotype of macrophages in tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 601.