Ganoderma lucidum extract decreases motility and lamellipodia formation of triple‐negative metastatic breast cancer

Abstract

Breast cancer (BC) is the leading cause of cancer among women in the United States and Puerto Rico. Triple‐negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, and lack of HER2 overexpression. Approximately, 15% of all women with TNBC typically display shorter overall survival and an early peak of distant recurrences at 3y after diagnosis. Treatments for TNBC are limited; currently, there are no approved targeted therapies besides non‐targeted chemotherapy. The mortality of TNBC could result from the lack of effective treatments to decrease the migration of cancer cells to other tissues. Hence, it its highly important to understand these migration processes and to find effective therapies. Therefore, we aimed to test the anti‐migration effects of the medicinal mushroom Ganoderma lucidumextract (GLE) on TNBC cell motility and on the regulation of proteins involved in this process. First, MDA‐MB‐231 cells were treated with various GLE concentrations and evaluated for cell viability and a washout assay. To study the effect of GLE on cell migration, cells were treated with vehicle, 0.25 or 0.96mg/mL (IC50) of GLE for 24h, followed by wound healing and invasion assays. The activity of Rac was tested by a pulldown activity assay and immunoblotting. Furthermore, we tested the expression of proteins important in the dynamics of cell motility Cdc42, Lamellipodin (Lpd), FAK, WAVE and Rho. The localization and expression of Lpd was visualized by immunocytochemistry. Results showed that GLE significantly decreased the cell viability on TNBC, with no cell recovery after a 72h period of treatment withdrawal. GLE significantly decreased MDA‐MB‐231 cell migration and invasion, while reducing the activity of Rac. The expression of Lpd, FAK, WAVE, c‐myc, and Cdc 42 were also modulated upon GLE treatment. GLE decreased Lpd localization in ruffled edges of cancer cells, as well as changes in nuclear and cell morphology. In conclusion, our results suggest the potential of GLE as a natural anti‐TNBC migration agent.Support or Funding InformationThis work was supported by grants from the National Institutes of Health GM111171 (MMM), MD007583 (MMM), GM103475 INBRE‐Supplies for Graduate Students (GOS), from the Puerto Rico Science, Technology and Research Trust (PRSTRT) SGRP 2017‐043, PRSTRT Hurricane Relief Funds, and from the U.S. Dept of Education Title‐V‐PPOHA P031M105050 and Title‐V‐Cooperative P031S130068. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Puerto Rico Science, Technology and Research Trust or the U.S. Department of Education.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.