Flavonoid Derivative of Cannabis Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer.
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Journal: 2019/August - Frontiers in Oncology
ISSN: 2234-943X
Abstract:
Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%. One of the significant barriers to effective treatment is the immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed. This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer. In vitro results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy. Meanwhile, in vivo results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials. Repeated experiments also showed significant (P < 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts. The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.
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Front Oncol 9: 660
PMID: 31396485

Flavonoid Derivative of <em>Cannabis</em> Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer

Figure S1

Structures of Cannabis flavonoids and the unnatural molecule FBL-03G. Through a bioactivity guided isolation approach, Cannflavin B (10) was isolated from a flavonoid rich fraction of Cannabis using flash chromatography along with 10 other compounds and characterized by NMR and MS spectroscopic methods. The spectroscopic data were similar to the data of the following 11 compounds previously isolated and characterized from the Cannabis plant; apigenin (1), Chrysoeriol (2), kaempferol (3), luteolin (4), quercetin (5), vitexin (6), isovitexin (7), orientin (8) and prenylated flavonoids including Cannflavin A (9), Cannflavin B (10), and Cannflavin C (11).

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Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
Department of Physics, University of Massachusetts Lowell, Lowell, MA, United States
Department of Biology, University of Massachusetts Boston, Boston, MA, United States
Department of CaNCURE Program, Northeastern University, Boston, MA, United States
Flavocure Biotech Inc., Baltimore, MD, United States
Edited by: Paul N. Span, Radboud University Nijmegen Medical Centre, Netherlands
Reviewed by: James William Jacobberger, Case Western Reserve University, United States; Hyuk-Jin Cha, Seoul National University, South Korea
*Correspondence: Wilfred Ngwa ude.dravrah.corl@awgnw
This article was submitted to Radiation Oncology, a section of the journal Frontiers in Oncology
Edited by: Paul N. Span, Radboud University Nijmegen Medical Centre, Netherlands
Reviewed by: James William Jacobberger, Case Western Reserve University, United States; Hyuk-Jin Cha, Seoul National University, South Korea
Received 2019 Mar 28; Accepted 2019 Jul 5.
Copyright © 2019 Moreau, Ibeh, Decosmo, Bih, Yasmin-Karim, Toyang, Lowe and Ngwa.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%. One of the significant barriers to effective treatment is the immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed. This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer. In vitro results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy. Meanwhile, in vivo results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials. Repeated experiments also showed significant (P < 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts. The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.

Keywords: pancreatic cancer, flavonoids, cannabis, metastasis, radiotherapy, smart biomaterials
Abstract

Acknowledgments

We thank all the members at Ngwa's lab at Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts for their support, and Servicebio Inc., Woburn, Massachusetts for technical support. Bio-Tech R&amp;D Institute, University of the West Indies, Mona, Jamaica is also acknowledged for its technical support.

Acknowledgments

Footnotes

Funding. Funding support for this work is acknowledged from the USA National Institutes of Health (NIH), grant number R21CA205094 and Flavocure Biotech Inc.

Footnotes
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