PMID- 23468988
OWN - NLM
STAT- MEDLINE
DCOM- 20130910
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 2
DP  - 2013
TI  - Anti-tumor effects of Ganoderma lucidum (reishi) in inflammatory breast cancer in 
      in vivo and in vitro models.
PG  - e57431
LID - 10.1371/journal.pone.0057431 [doi]
LID - e57431
AB  - The medicinal mushroom Ganoderma lucidum (Reishi) was tested as a potential 
      therapeutic for Inflammatory Breast Cancer (IBC) using in vivo and in vitro IBC 
      models. IBC is a lethal and aggressive form of breast cancer that manifests 
      itself without a typical tumor mass. Studies show that IBC tissue biopsies 
      overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI), two 
      proteins that are partially responsible for the unique pathological properties of 
      this disease. IBC is treated with a multimodal approach that includes 
      non-targeted systemic chemotherapy, surgery, and radiation. Because of its 
      non-toxic and selective anti-cancer activity, medicinal mushroom extracts have 
      received attention for their use in cancer therapy. Our previous studies 
      demonstrate these selective anti-cancer effects of Reishi, where IBC cell 
      viability and invasion, as well as the expression of key IBC molecules, including 
      eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi 
      focusing on the phosphoinositide-3-kinase (PI3K)/AKT/mammalian target of 
      rapamycin (mTOR) pathway, a regulator of cell survival and growth. The present 
      study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression 
      of mTOR downstream effectors at early treatment times, as we observe reduced 
      eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with 
      consequential protein synthesis reduction. Severe combined immunodeficient mice 
      injected with IBC cells treated with Reishi for 13 weeks show reduced tumor 
      growth and weight by  approximately 50%, and Reishi treated tumors showed reduced expression of 
      E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated 
      kinase (ERK1/2). Our results provide evidence that Reishi suppresses protein 
      synthesis and tumor growth by affecting survival and proliferative signaling 
      pathways that act on translation, suggesting that Reishi is a potential natural 
      therapeutic for breast and other cancers.
FAU - Suarez-Arroyo, Ivette J
AU  - Suarez-Arroyo IJ
AD  - Department of Biochemistry, Universidad Central del Caribe, School of Medicine, 
      Bayamon, Puerto Rico, United States of America.
FAU - Rosario-Acevedo, Raysa
AU  - Rosario-Acevedo R
FAU - Aguilar-Perez, Alexandra
AU  - Aguilar-Perez A
FAU - Clemente, Pedro L
AU  - Clemente PL
FAU - Cubano, Luis A
AU  - Cubano LA
FAU - Serrano, Juan
AU  - Serrano J
FAU - Schneider, Robert J
AU  - Schneider RJ
FAU - Martinez-Montemayor, Michelle M
AU  - Martinez-Montemayor MM
LA  - eng
GR  - P031M105050/PHS HHS/United States
GR  - SC3 GM111171/GM/NIGMS NIH HHS/United States
GR  - 2G12RR003035/RR/NCRR NIH HHS/United States
GR  - G12 RR003035/RR/NCRR NIH HHS/United States
GR  - 8G12MD007583/MD/NIMHD NIH HHS/United States
GR  - G12 MD007583/MD/NIMHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130228
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA Primers)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Base Sequence
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - DNA Primers
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Inflammatory Breast Neoplasms/metabolism/pathology/*therapy
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Reishi/*chemistry
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3585368
COIS- Competing Interests: Dr. Juan Serrano is a pathologist at San Pablo Pathology who 
      sectioned the tumors from the mice used in this study. Once the animals were 
      euthanized, the authors provided Dr. Serrano the tumors in formalin where he 
      sectioned and mounted them onto slides. He did not know what tumor belonged to 
      what treatment. This does not alter the authors' adherence to all the PLOS ONE 
      policies on sharing data and materials.
EDAT- 2013/03/08 06:00
MHDA- 2013/09/11 06:00
PMCR- 2013/02/28
CRDT- 2013/03/08 06:00
PHST- 2012/09/06 00:00 [received]
PHST- 2013/01/22 00:00 [accepted]
PHST- 2013/03/08 06:00 [entrez]
PHST- 2013/03/08 06:00 [pubmed]
PHST- 2013/09/11 06:00 [medline]
PHST- 2013/02/28 00:00 [pmc-release]
AID - PONE-D-12-27319 [pii]
AID - 10.1371/journal.pone.0057431 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(2):e57431. doi: 10.1371/journal.pone.0057431. Epub 2013 Feb 28.