Abstract 231: The polyphenolic plant lignan secoisolariciresinol diglycoside reduces mammary tumor growth, possibly via inhibition of local inflammatory signaling

Abstract

Background: Secoisolariciresinol diglycoside (SDG) is a polyphenolic plant lignan found in flax and sesame seeds as well as legumes, whole grains, fruits and vegetables. It is metabolized by the gut bacteria into two major enterolignans: enterolactone (ENL) and enterodiol (END). These enterolignans have been associated with reduced breast cancer risk and progression in population studies as well as decreased tumor growth in preclinical models of breast cancer. Methods: The impact of SDG supplementation on tumor growth in a mouse model of basal-like breast cancer was examined. C57BL/6 mice were fed a control diet (10% kcal from fat) or control diet with SDG supplementation (100 mg/kg food) for eight weeks, then both groups were orthotopically injected with E0771 mammary tumor cells. An inflammatory signaling qPCR array (Qiagen) was performed on mammary tissue distal to tumor. Tumors were stained by immunohistochemistry (IHC) for Ki67 to measure proliferation levels and phospho-p65 to determine inflammatory signaling pathway activation. Tumors and mammary tissue were also stained for F4/80 to quantify macrophage infiltration. Serum level of hormones, adipokines, and cytokines were measured via luminex assay (Bio-Rad). Results: SDG supplementation significantly decreased tumor weight (p<0.05). SDG did not affect body weight or body fat percentage but did significantly decrease expression of F4/80, CRP, and other pro-inflammatory markers in the mammary tissue. IHC staining revealed no difference in tumor proliferation; however, SDG supplementation did reduce inflammatory signaling in the tumors, indicated by a significant decrease in phospho-p65 staining. However, serum cytokine levels were not significantly different between the groups. Tumors are currently being stained by IHC for cleaved caspase 3 to measure levels of apoptosis. In addition, cell culture experiments will be conducted to define the impact of ENL treatment on protumorigenic cross-talk between tumor cells, adipocytes, and macrophages. Specifically, the effects of conditioned media from adipocyte/macrophage co-cultures (with +/- ENL treatment) on mouse E0771 and human MDA-MB-231 tumor cell proliferation, migration and invasion will be examined. Conclusions: SDG supplementation reduced mammary tumor growth in association with SDG’s effects on local, but not systemic, inflammatory signaling. Citation Format: Claire G. Lineberger, Laura W. Bowers, Nikki A. Ford, Emily L. Rossi, Bruce K. Kimler, Carol J. Fabian, Stephen D. Hursting. The polyphenolic plant lignan secoisolariciresinol diglycoside reduces mammary tumor growth, possibly via inhibition of local inflammatory signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 231. doi:10.1158/1538-7445.AM2017-231

A combination of metabolite profiling and network pharmacology to explore the potential pharmacological changes of secoisolariciresinol-diglycoside

“…Secoisolariciresinol-diglycoside (SDG), a polyphenolic plant lignan, was characterized as one of the major compounds found in axseeds. It exerts serious activities of anti-depression, 3 antitumor, 4 anti-prostatic hyperplasia 5 and analgesic effects, 6 etc. In previous work, the pharmacokinetic kinetics of SDG and its two metabolites (secoisolariciresinol and enterodiol) aer oral administration were reported.…”