Abstract 2894: Impact of honokiol on sialylation in breast cancer cells

Abstract

Abstract Metastasis is a process in which malignant cells spread form the tumor of origin and colonize at distant organs. One of the diagnostic markers of metastatic progression is the overexpression of a transmembrane protein called Mucin 1 (MUC1). High levels of MUC1 have been found in tumor tissues, including breast cancer, and have been implicated in reduced survival rate. After translation of the protein, carbohydrate groups are attached to MUC1, a process called glycosylation. The resulting glycocalyx, which serves as a protective layer on epithelial surfaces, is involved in cell-cell interactions, signaling and metastasis. Glycosylation patterns differ on MUC1 in normal breast tissue in comparison with MUC1 in breast tumors. Not only do breast tumors have simpler and fewer carbohydrate chains than MUC1 from normal breast epithelial tissue, they also have increased levels of the carbohydrate derivative, sialic acid. Altered addition of sialic acid (sialylation) has been associated with cancer transformation and metastatic progression of the disease. The enzyme, α-2,3 sialyltransferase (ST3Gal I) which adds the α-2,3-linked sialic acids to MUC1 is increased in breast tumors and has been correlated with poor prognosis. Shortening of the carbohydrates units on MUC1 in breast tumors unmasks peptides that would otherwise be covered by the carbohydrates in normal MUC1, and current studies seek to identify antibodies that would directly target MUC1 on the cancer cells and in turn prevent cancer metastasis. Plant derived natural product honokiol is being studied for its anti-tumor activities. To assess the effect of honokiol on ST3Gal I, we treated breast cancer cell lines, MDA-MB-231 and MCF-7 cells with honokiol and analyzed its effect on ST3Gal I mRNA and protein expression using RT-PCR and Western Blotting, respectively. Honokiol suppressed ST3Gal I at the mRNA and protein level in both cancer cell lines. To investigate specifically whether honokiol reduces free sialic acid, we treated mammary carcinoma cells with honokiol and using the Sialic Acid Kit, we observed reduction in sialic acid in honokiol-treated mammary carcinoma cells. Future immunoprecipitation studies are underway to investigate specifically whether honokiol suppresses sialylation of MUC1. We propose that these studies will lead to the understanding on how sialylation of MUC1 alters the cellular signaling processes involved in the transformation of breast cancer and eventually to the spread of the disease. Citation Format: Padmamalini Thulasiraman, Galen Garriga. Impact of honokiol on sialylation in breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2894.