Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns

BMC Cancer
Kerstin Maria Kampa-SchittenhelmMarcus Matthias Schittenhelm

Abstract

It has been previously demonstrated in several cancer models, that Dronabinol (THC) may have anti-tumor activity--however, controversial data exists for acute leukemia. We have anecdotal evidence that THC may have contributed to disease control in a patient with acute undifferentiated leukemia. To test this hypothesis, we evaluated the antileukemic efficacy of THC in several leukemia cell lines and native leukemia blasts cultured ex vivo. Expression analysis for the CB1/2 receptors was performed by Western immunoblotting and flow cytometry. CB-receptor antagonists as well as a CRISPR double nickase knockdown approach were used to evaluate for receptor specificity of the observed proapoptotic effects. Meaningful antiproliferative as well as proapoptotic effects were demonstrated in a subset of cases--with a preference of leukemia cells from the lymphatic lineage or acute myeloid leukemia cells expressing lymphatic markers. Induction of apoptosis was mediated via CB1 as well as CB2, and expression of CB receptors was a prerequisite for therapy response in our models. Importantly, we demonstrate that antileukemic concentrations are achievable in vivo. Our study provides rigorous data to support clinical evaluation of THC as a low-...Continue Reading

References

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May 28, 2013·Molecular Cancer·Kerstin Maria Kampa-SchittenhelmMarcus Matthias Schittenhelm
Jan 30, 2014·Case Reports in Oncology·Yadvinder Singh, Chamandeep Bali

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Citations

Sep 14, 2016·British Journal of Haematology·Han Zhang, Nami McCarty
Mar 1, 2017·Pediatric Blood & Cancer·Caroline DiorioStacey Marjerrison
May 15, 2020·International Journal of Molecular Sciences·Dorian ForteLucia Catani
Jul 19, 2018·BMC Biotechnology·Adrián MontañoRocío Benito
Nov 28, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Samridhi LalSubash C Gupta
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Natasha IrreraAlessandro Allegra

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Methods Mentioned

BETA
flow cytometry
transfection
PCR

Software Mentioned

Prism
CellQuest®
Graph Pad

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