Tamoxifen Sensitizes Acute Lymphoblastic Leukemia Cells to Cannabidiol by Targeting Cyclophilin-D and Altering Mitochondrial Ca2+ Homeostasis

Autor: Zeferino Gómez-Sandoval, Kathya Villatoro-Gómez, Oxana Dobrovinskaya, Miguel Olivas-Aguirre, Igor Pottosin, Liliana Torres-López
Rok vydání: 2021
Předmět:
Models
Molecular
Protein Conformation
QH301-705.5
acute lymphoblastic leukemia
Mitochondrion
Article
Catalysis
Inorganic Chemistry
Jurkat Cells
cannabidiol
chemistry.chemical_compound
stomatognathic system
Cell Line
Tumor
medicine
Homeostasis
Humans
Cytotoxic T cell
Biology (General)
Physical and Theoretical Chemistry
skin and connective tissue diseases
QD1-999
Molecular Biology
Spectroscopy
Membrane Potential
Mitochondrial
Membrane potential
tamoxifen
MPTP
Organic Chemistry
mitochondrial permeability transition pore
Drug Synergism
General Medicine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
digestive system diseases
Computer Science Applications
Molecular Docking Simulation
mitochondria
Chemistry
surgical procedures
operative
Mitochondrial permeability transition pore
chemistry
Cancer research
Calcium
cyclophilin D
Cannabidiol
hormones
hormone substitutes
and hormone antagonists
Tamoxifen
calcium overload
medicine.drug
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 8688, p 8688 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 16
ISSN: 1422-0067
DOI: 10.3390/ijms22168688
Popis: 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.
Databáze: OpenAIRE
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