Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Oncol. 2015 Apr;9(4):906-19. doi: 10.1016/j.molonc.2014.12.010. Epub 2015 Jan 19.

Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: novel anti-tumor mechanisms of Cannabidiol in breast cancer.

Author information

  • 1Department of Pathology, The Ohio State University, Wexner Medical Center, 43210, USA; The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: elbaz.2@osu.edu.
  • 2Department of Pathology, The Ohio State University, Wexner Medical Center, 43210, USA; The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: Mohd.Nasser@osumc.edu.
  • 3Department of Pathology, The Ohio State University, Wexner Medical Center, 43210, USA; The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: Janani.Ravi@osumc.edu.
  • 4Department of Pathology, The Ohio State University, Wexner Medical Center, 43210, USA; The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: Nissar.Wani@osumc.edu.
  • 5Department of Pathology, The Ohio State University, Wexner Medical Center, 43210, USA; The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: Dinesh.Ahirwar@osumc.edu.
  • 6Department of Pathology, The Ohio State University, Wexner Medical Center, 43210, USA; The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: Helong.Zhao@osumc.edu.
  • 7Department of Pathology, The Ohio State University, Wexner Medical Center, 43210, USA; The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: Steve.Oghumu@osumc.edu.
  • 8Department of Pathology, The Ohio State University, Wexner Medical Center, 43210, USA; The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: abhay.satoskar@osumc.edu.
  • 9Department of Pathology, The Ohio State University, Wexner Medical Center, 43210, USA; The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: Konstantin.Shilo@osumc.edu.
  • 10The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA; Department of Surgery, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: carson.77@osu.edu.
  • 11Department of Pathology, The Ohio State University, Wexner Medical Center, 43210, USA; The Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, 43210, USA. Electronic address: Ramesh.ganju@osumc.edu.

Abstract

The anti-tumor role and mechanisms of Cannabidiol (CBD), a non-psychotropic cannabinoid compound, are not well studied especially in triple-negative breast cancer (TNBC). In the present study, we analyzed CBD's anti-tumorigenic activity against highly aggressive breast cancer cell lines including TNBC subtype. We show here -for the first time-that CBD significantly inhibits epidermal growth factor (EGF)-induced proliferation and chemotaxis of breast cancer cells. Further studies revealed that CBD inhibits EGF-induced activation of EGFR, ERK, AKT and NF-kB signaling pathways as well as MMP2 and MMP9 secretion. In addition, we demonstrated that CBD inhibits tumor growth and metastasis in different mouse model systems. Analysis of molecular mechanisms revealed that CBD significantly inhibits the recruitment of tumor-associated macrophages in primary tumor stroma and secondary lung metastases. Similarly, our in vitro studies showed a significant reduction in the number of migrated RAW 264.7 cells towards the conditioned medium of CBD-treated cancer cells. The conditioned medium of CBD-treated cancer cells also showed lower levels of GM-CSF and CCL3 cytokines which are important for macrophage recruitment and activation. In summary, our study shows -for the first time-that CBD inhibits breast cancer growth and metastasis through novel mechanisms by inhibiting EGF/EGFR signaling and modulating the tumor microenvironment. These results also indicate that CBD can be used as a novel therapeutic option to inhibit growth and metastasis of highly aggressive breast cancer subtypes including TNBC, which currently have limited therapeutic options and are associated with poor prognosis and low survival rates.

Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Cannabidiol; EGFR; Triple negative breast cancer; Tumor microenvironment

PMID:
25660577
[PubMed - indexed for MEDLINE]
PMCID:
PMC4387115
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk