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Canna~Fangled Abstracts

Tamoxifen Sensitizes Acute Lymphoblastic Leukemia Cells to Cannabidiol by Targeting Cyclophilin-D and Altering Mitochondrial Ca 2+ Homeostasis

By August 14, 2021August 30th, 2021No Comments

 

. 2021 Aug 13;22(16):8688.

doi: 10.3390/ijms22168688.

Miguel Olivas-Aguirre 1, Liliana Torres-López 1, Zeferino Gómez-Sandoval 2, Kathya Villatoro-Gómez 1, Igor Pottosin 1, Oxana Dobrovinskaya 1
Affiliations 

Abstract

Cytotoxic effects of cannabidiol (CBD) and tamoxifen (TAM) have been observed in several cancer types. We have recently shown that CBD primarily targets mitochondria, inducing a stable mitochondrial permeability transition pore (mPTP) and, consequently, the death of acute lymphoblastic leukemia (T-ALL) cells. Mitochondria have also been documented among cellular targets for the TAM action. In the present study we have demonstrated a synergistic cytotoxic effect of TAM and CBD against T-ALL cells. By measuring the mitochondrial membrane potential (ΔΨm), mitochondrial calcium ([Ca2+]m) and protein-ligand docking analysis we determined that TAM targets cyclophilin D (CypD) to inhibit mPTP formation. This results in a sustained [Ca2+]m overload upon the consequent CBD administration. Thus, TAM acting on CypD sensitizes T-ALL to mitocans such as CBD by altering the mitochondrial Ca2+ homeostasis.

 

Keywords: acute lymphoblastic leukemia, calcium overload, cannabidiol, cyclophilin D, mitochondria, mitochondrial permeability transition pore, tamoxifen

Conflict of interest statement

The authors declare no conflict of interest.

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References

    1. Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. Cancer statistics, 2021. CA Cancer J. Clin. 2021;71:7–33. doi: 10.3322/caac.21654. – DOI – PubMed
    1. Raetz E.A., Teachey D.T. T-cell acute lymphoblastic leukemia. Hematol. Am. Soc. Hematol. Educ. Program. 2016;2016:580–588. doi: 10.1182/asheducation-2016.1.580. – DOI – PMC – PubMed
    1. Inaba H., Pui C.H. Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia. J. Clin. Med. 2021;10:1926. doi: 10.3390/jcm10091926. – DOI – PMC – PubMed
    1. Aster J.C., DeAngelo D.J. Resistance revealed in acute lymphoblastic leukemia. Nat. Med. 2013;19:264–265. doi: 10.1038/nm.3119. – DOI – PubMed
    1. Pillozzi S., Masselli M., De Lorenzo E., Accordi B., Cilia E., Crociani O., Amedei A., Veltroni M., D’Amico M., Basso G., et al. Chemotherapy resistance in acute lymphoblastic leukemia requires hERG1 channels and is overcome by hERG1 blockers. Blood. 2011;117:902–914. doi: 10.1182/blood-2010-01-262691. – DOI – PubMed

 

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