Abstract 5548: Reishi reduces the phosphorylation of STAT-3 in inflammatory breast cancer in vitro and in vivo models

Inflammatory Breast Cancer (IBC) is an aggressive form of breast cancer (BC) with symptoms that include a diffuse redness and swelling of the breast. Pathological findings indicate the presence of tumor emboli (tumor spheroids in vitro) invading the dermal lymphatics of the breast; a process considered to be responsible for the inflammatory phenotype seen in this disease. However, these tumors produce inflammatory mediators such interleukin-6 (IL-6), which may act as growth factors that contribute with cancer progression. Some consequences of IL-6 activation include the activation of the Janus Kinase-2/Signal Transducer and Activator of Transcription 3 (STAT-3) pathway that results in triggering invasion and metastasis processes. Our published data demonstrates that the medicinal mushroom, Ganoderma lucidum (Reishi), disintegrates tumor emboli, reduces tumor growth and modulates the abundance of proteins involved in invasion cascades. In the current study, we assessed the effects of Reishi on inflammatory markers focusing on the IL-6/JAK-2/STAT-3 pathway both in vitro and in vivo. SUM-149 IBC and SUM-102 non-IBC BC cells were treated with vehicle, or Reishi at different time points to determine cancer cell viability, invasion via three-dimensional culture assays and protein abundance via immunoblots. In vivo studies were carried out in female severe combined immunodeficient (SCID) mice that were injected with SUM-149 IBC cells in their lower right mammary fat pad and then treated with vehicle, 7mg/kgBW, or 14mg/kgBW Reishi for 10wk. Our data from the in vitro study suggests that Reishi reduces cancer cell viability, and Reishi has an immunomodulatory role in SUM-149 IBC cell line, demonstrated by its ability to reduce the secretion of IL-6 and reduced phosphorylation of STAT-3 in SUM-149 cells. Cell invasion studies show that Reishi reduces invasion in IBC cells. Interestingly, Reishi reduces SUM-102 BC cell viability; however it does not affect STAT-3 signaling in the cell line. Our in vivo results show that Reishi deceases tumor volume by 46 and 77%, when treated with 7mg/kgBW, or 14mg/kgBW Reishi, respectively. Moreover, the phosphorylation of STAT-3 in tumor lysates significantly decreases in a concentration dependent manner. Our data suggests that Reishi inactivates STAT-3 both in vitro and in vivo in IBC cells, thus Reishi may be used as a targeted therapeutic for women afflicted with IBC, for whom no direct therapeutics are currently available. This