PMID- 35018819
OWN - NLM
STAT- MEDLINE
DCOM- 20220502
LR  - 20230302
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 322
IP  - 3
DP  - 2022 Mar 1
TI  - Emodin reduces tumor burden by diminishing M2-like macrophages in colorectal 
      cancer.
PG  - G383-G395
LID - 10.1152/ajpgi.00303.2021 [doi]
AB  - Emodin, a natural anthraquinone, has been shown to have antitumorigenic 
      properties and may be an effective therapy for colorectal cancer (CRC). However, 
      its clinical development has been hampered by a poor understanding of its 
      mechanism of action. The purpose of this study was to 1) evaluate the efficacy of 
      emodin in mouse models of intestinal/colorectal cancer and 2) to examine the 
      impact of emodin on macrophage behavior in the context of CRC. We used a genetic 
      model of intestinal cancer (Apc(Min/+)) and a chemically induced model of CRC 
      [azoxymethane/dextran sodium sulfate (AOM/DSS)]. Emodin was administered orally 
      (40 or 80 mg/kg in AOM/DSS and 80 mg/kg in Apc(Min/+)) three times a week to 
      observe its preventative effects. Emodin reduced polyp count and size in both 
      rodent models (P < 0.05). We further analyzed the colon microenvironment of 
      AOM/DSS mice and found that mice treated with emodin exhibited lower 
      protumorigenic M2-like macrophages and a reduced ratio of M2/M1 macrophages 
      within the colon (P < 0.05). Despite this, we did not detect any significant 
      changes in M2-associated cytokines (IL10, IL4, and Tgfb1) nor M1-associated 
      cytokines (IL6, TNFalpha, IL1beta, and IFNgamma) within excised polyps. However, there was a 
      significant increase in NOS2 expression (M1 marker) in mice treated with 80 mg/kg 
      emodin (P < 0.05). To confirm emodin's effects on macrophages, we exposed bone 
      marrow-derived macrophages (BMDMs) to C26 colon cancer cell conditioned media. 
      Supporting our in vivo data, emodin reduced M2-like macrophages. Overall, these 
      data support the development of emodin as a natural compound for prevention of 
      CRC given its ability to target protumor macrophages.NEW & NOTEWORTHY Our study 
      confirms that emodin is an effective primary therapy against the onset of genetic 
      and chemically induced sporadic colorectal cancer. We established that emodin 
      reduces the M2-like protumorigenic macrophages in the tumor microenvironment. 
      Furthermore, we provide evidence that emodin may be acting to antagonize the P2X7 
      receptor within the bone tissue and consequently decrease the activation of 
      proinflammatory cells, which may have implications for recruitment of cells to 
      the tumor microenvironment.
FAU - Sougiannis, Alexander T
AU  - Sougiannis AT
AD  - Department of Pathology, Microbiology, and Immunology, University of South 
      Carolina School of Medicine, Columbia, South Carolina.
AD  - College of Medicine, Medical University of South Carolina, Columbia, South 
      Carolina.
FAU - VanderVeen, Brandon
AU  - VanderVeen B
AD  - Department of Pathology, Microbiology, and Immunology, University of South 
      Carolina School of Medicine, Columbia, South Carolina.
AD  - AcePre, LLC, Columbia, South Carolina.
FAU - Chatzistamou, Ioulia
AU  - Chatzistamou I
AD  - Department of Pathology, Microbiology, and Immunology, University of South 
      Carolina School of Medicine, Columbia, South Carolina.
FAU - Kubinak, Jason L
AU  - Kubinak JL
AD  - Department of Pathology, Microbiology, and Immunology, University of South 
      Carolina School of Medicine, Columbia, South Carolina.
FAU - Nagarkatti, Mitzi
AU  - Nagarkatti M
AD  - Department of Pathology, Microbiology, and Immunology, University of South 
      Carolina School of Medicine, Columbia, South Carolina.
FAU - Fan, Daping
AU  - Fan D
AD  - Department of Cell Biology and Anatomy, University of South Carolina School of 
      Medicine, Columbia, South Carolina.
AD  - AcePre, LLC, Columbia, South Carolina.
FAU - Murphy, E Angela
AU  - Murphy EA
AUID- ORCID: 0000-0002-4803-5822
AD  - Department of Pathology, Microbiology, and Immunology, University of South 
      Carolina School of Medicine, Columbia, South Carolina.
AD  - AcePre, LLC, Columbia, South Carolina.
LA  - eng
GR  - R01 CA218578/CA/NCI NIH HHS/United States
GR  - R41 AT009964/AT/NCCIH NIH HHS/United States
GR  - F31 AT009820/AT/NCCIH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20220112
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Cytokines)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - KA46RNI6HN (Emodin)
RN  - MO0N1J0SEN (Azoxymethane)
SB  - IM
MH  - Animals
MH  - Azoxymethane
MH  - *Colonic Neoplasms/pathology
MH  - *Colorectal Neoplasms/pathology
MH  - Cytokines/metabolism
MH  - Dextran Sulfate/pharmacology
MH  - *Emodin/metabolism/pharmacology/therapeutic use
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Signal Transduction
MH  - Tumor Burden
MH  - Tumor Microenvironment
PMC - PMC8897011
OTO - NOTNLM
OT  - colorectal cancer
OT  - emodin
OT  - macrophages
OT  - mouse models
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2022/01/13 06:00
MHDA- 2022/05/03 06:00
PMCR- 2023/03/01
CRDT- 2022/01/12 08:41
PHST- 2022/01/13 06:00 [pubmed]
PHST- 2022/05/03 06:00 [medline]
PHST- 2022/01/12 08:41 [entrez]
PHST- 2023/03/01 00:00 [pmc-release]
AID - GI-00303-2021 [pii]
AID - 10.1152/ajpgi.00303.2021 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2022 Mar 1;322(3):G383-G395. doi: 
      10.1152/ajpgi.00303.2021. Epub 2022 Jan 12.