Ganoderma lucidum extract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway
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Tiffany J. Rios-Fuller1, Gabriela Ortiz-Soto1, Mercedes Lacourt-Ventura1, Gerónimo Maldonado-Martinez1, Luis A. Cubano1, Robert J. Schneider2 and Michelle M. Martinez-Montemayor1
1Universidad Central del Caribe-School of Medicine, Bayamon, Puerto Rico, United States of America
2NYU School of Medicine, New York, New York, United States of America
Michelle M. Martinez-Montemayor, email: [email protected]
Keywords: triple negative breast cancer; cancer stem cells; aldehyde dehydrogenase; Ganoderma lucidum extract; STAT3
Received: June 30, 2018 Accepted: October 24, 2018 Published: November 13, 2018
The aggressive nature of triple negative breast cancer (TNBC) may be explained in part by the presence of breast cancer stem cells (BCSCs), a subpopulation of cells, which are involved in tumor initiation, progression, metastasis, recurrence, and therapy resistance. The signal transducer and activator of transcription 3 (STAT3) pathway participates in the development and progression of BCSCs, but its role in TNBC remains unclear. Here, we report that Ganoderma lucidum extract (GLE), a medicinal mushroom with anticancer activity, acts on BCSCs in vitro and in TNBC pre-clinical animal tumor models by downregulating the STAT3 pathway. We show that GLE significantly reduces TNBC cell viability, and down-regulates total and phosphorylated STAT3 expression. This is consistent with the reduction of OCT4, NANOG and SOX2 expression, reduction in the BCSC population by loss of the ALDH1 and CD44+/CD24– population, the deformation of mammospheres, and the strong reduction in animal tumor volume and tumor weight. Analysis of the BCSC compartment in tumors revealed that GLE decreases the STAT3 pathway and the expression of OCT4, NANOG, and SOX2 in BCSCs. These findings demonstrate that the anti-cancer activity of GLE targets BCSCs of TNBC through the downregulation of the STAT3 pathway.
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