Abstract 2247: Ganoderma lucidum (Reishi) downregulates key proteins overexpressed in IBC and chemosensitizes EGFR-overexpressing cells to erlotinib.

Abstract

Abstract Inflammatory Breast Cancer (IBC) is a unique and aggressive cancer where tumor spheroids invade the dermal lymphatics causing the inflammatory phenotype. IBC cell lines and human tissues overexpress plasma membrane proteins such as E-cadherin and Epidermal Growth Factor Receptor (EGFR), which are associated with maintaining tumor spheroid integrity, increased IBC tumor growth rate, invasion and metastasis. Since IBC tumor cell emboli are more efficient at forming metastases and are more resistant to chemo and radiotherapy than single cells, it seems feasible to prevent IBC with a compound that has the ability to disintegrate the cell spheroids. Our published data shows that the medicinal mushroom, Ganoderma lucidum (Reishi), inhibits IBC progression via disintegration of tumor spheroids. Thus, we aimed to investigate Reishi's in vitro and in vivo therapeutic potential in IBC, focusing on the regulation of E-cadherin and EGFR and its contribution to the IBC cellular response when treated with the EGFR Tyrosine Kinase Inhibitor (TKI), erlotinib (commercially known as Tarceva®). Herein, we show that Reishi downregulates E-cadherin and EGFR abundance in vitro, significantly reduces tumor growth by 58%, and downregulates in vivo EGFR, and E-cadherin protein expression. Moreover, a synergistic effect is observed when erlotinib and Reishi are used simultaneously after 72 hours of treatment. Since Reishi downregulates the expression of E-cadherin and EGFR, our subsequent investigations will focus on the identification of PM proteins using stable isotope labeling with amino acids in cell culture (SILAC). Our results provide evidence that Reishi downregulates key proteins overexpressed in IBC, and chemosensitizes IBC cells to erlotinib therapy, highlighting its anti-IBC-therapeutic potential. This project was sponsored by Title V PPOHA US Dept of Education #P031M105050 to UCC, NIH/RCMI #2G12RR003035 to UCC, NIH/INBRE #5P20RR016470 to UPR/UCC, NIH/NCRR #U54RR026139 to UPR/UCC, and a research donation from the Commonwealth of Puerto Rico to UCC-Centro Universitario de Medicina Integral y Complementaria (CUMIC) / MMM. Citation Format: Ivette Suarez-Arroyo, Raysa Rosario-Acevedo, Alexandra Aguilar-Pérez, Luis A. Cubano, Michelle M. Martínez-Montemayor. Ganoderma lucidum (Reishi) downregulates key proteins overexpressed in IBC and chemosensitizes EGFR-overexpressing cells to erlotinib. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2247. doi:10.1158/1538-7445.AM2013-2247