Ganoderma lucidum Extract Reduces the Motility of Breast Cancer Cells Mediated by the RAC⁻Lamellipodin Axis.

Ariana Acevedo-Díaz,Ivette J Suárez-Arroyo,Michelle M Martínez Montemayor,Astrid Zayas-Santiago,Gabriela Ortiz-Soto

doi:10.3390/nu11051116

Ariana Acevedo-Díaz, Ivette J Suárez-Arroyo + Show 3 more

Open Access

https://doi.org/10.3390/nu11051116

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Abstract

Breast cancer (BC) is the second leading cause of cancer death among women worldwide. The main cause of BC morbidity and mortality is the invasiveness capacity of cancer cells that may lead to metastasis. Here, we aimed to investigate the therapeutic efficacy of Ganoderma lucidum extract (GLE)—a medicinal mushroom with anticancer properties—on BC motility via the Rac/Lamellipodin pathway. GLE treatment effects were tested on MDA-MB-231 breast cancer cells. The effects were tested on cell viability, migration and invasion. Pulldowns, immunoblotting, and immunofluorescence were used to measure Rac activity and the expression of proteins involved in cell migration and in lamellipodia formation, respectively. As a result, GLE suppressed BC cell viability, migration, and invasion capacity. GLE impaired Rac activity, as well as downregulated Lamellipodin, ENA/VASP, p-FAK (Tyr925), Cdc42, and c-Myc expression. Lamellipodia formation was significantly reduced by GLE. In conclusion, we demonstrate that GLE reduces Rac activity and downregulates signaling molecules involved in lamellipodia formation. These novel findings serve as basis for further studies to elucidate the potential of GLE as a therapeutic agent regulating the Rac/Lamellipodin pathway in BC metastasis.

Highlights

Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer death among women worldwide [1,2]
We investigated the therapeutic efficacy of Ganoderma lucidum extract (GLE)
These results agree manner in the highly aggressive and invasive triple-negative BC cell line MDA-MB-231. These results with previous findings from our group established that GLE dose-dependently reduces the agree with previous findings from ourwhere groupwe where we established that GLE dose-dependently cell viability of other highly invasive cells (MDA-MB-468, MDA-MB-435, SUM-102, and reduces the cell viability of other highly invasive BC cells (MDA-MB-468, MDA-MB-435, SUM-102, in a dose-dependent manner by various mechanisms including via apoptosis induction and SUM-149) in a dose-dependent manner by various mechanisms including via apoptosis

Summary

Introduction

Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer death among women worldwide [1,2]. Cancer metastasis comprises numerous interdependent processes, which include uncontrolled growth of cancer cells, invasion to surrounding tissues, migration to distant sites of the body, and colonization of other organs [3]. Among these processes, abnormal regulation of cell migration plays a critical role promoting the dissemination of cancer cells from the primary tumor to other distant tissues [4,5]. Migratory cells undertake molecular and cellular changes including the remodeling of their cell-cell and cell–matrix adhesion and their actin cytoskeleton which comprises molecular processes involving the activity of various

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