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Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia.
Cell Death Dis. 2019 10 14; 10(10):779.CD

Abstract

Anticancer properties of non-psychoactive cannabinoid cannabidiol (CBD) have been demonstrated on tumors of different histogenesis. Different molecular targets for CBD were proposed, including cannabinoid receptors and some plasma membrane ion channels. Here we have shown that cell lines derived from acute lymphoblastic leukemia of T lineage (T-ALL), but not resting healthy T cells, are highly sensitive to CBD treatment. CBD effect does not depend on cannabinoid receptors or plasma membrane Ca2+-permeable channels. Instead, CBD directly targets mitochondria and alters their capacity to handle Ca2+. At lethal concentrations, CBD causes mitochondrial Ca2+ overload, stable mitochondrial transition pore formation and cell death. Our results suggest that CBD is an attractive candidate to be included into chemotherapeutic protocols for T-ALL treatment.

Authors+Show Affiliations

Laboratory of Immunobiology and Ionic Transport Regulation, University Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Col. 28030, Colima, Mexico.Laboratory of Immunobiology and Ionic Transport Regulation, University Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Col. 28030, Colima, Mexico.Laboratory of Immunobiology and Ionic Transport Regulation, University Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Col. 28030, Colima, Mexico.Department of Cognitive Neuroscience and National Laboratory of Channelopathies (LaNCa), Institute of Cellular Physiology, National Autonomous University of Mexico, Mexico-City, Mexico.Laboratory of Immunobiology and Ionic Transport Regulation, University Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Col. 28030, Colima, Mexico. pottosin@ucol.mx.Laboratory of Immunobiology and Ionic Transport Regulation, University Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Col. 28030, Colima, Mexico. oxana@ucol.mx.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31611561

Citation

Olivas-Aguirre, Miguel, et al. "Cannabidiol Directly Targets Mitochondria and Disturbs Calcium Homeostasis in Acute Lymphoblastic Leukemia." Cell Death & Disease, vol. 10, no. 10, 2019, p. 779.
Olivas-Aguirre M, Torres-López L, Valle-Reyes JS, et al. Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia. Cell Death Dis. 2019;10(10):779.
Olivas-Aguirre, M., Torres-López, L., Valle-Reyes, J. S., Hernández-Cruz, A., Pottosin, I., & Dobrovinskaya, O. (2019). Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia. Cell Death & Disease, 10(10), 779. https://doi.org/10.1038/s41419-019-2024-0
Olivas-Aguirre M, et al. Cannabidiol Directly Targets Mitochondria and Disturbs Calcium Homeostasis in Acute Lymphoblastic Leukemia. Cell Death Dis. 2019 10 14;10(10):779. PubMed PMID: 31611561.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia. AU - Olivas-Aguirre,Miguel, AU - Torres-López,Liliana, AU - Valle-Reyes,Juan Salvador, AU - Hernández-Cruz,Arturo, AU - Pottosin,Igor, AU - Dobrovinskaya,Oxana, Y1 - 2019/10/14/ PY - 2019/05/21/received PY - 2019/09/24/accepted PY - 2019/08/22/revised PY - 2019/10/16/entrez PY - 2019/10/16/pubmed PY - 2020/8/22/medline SP - 779 EP - 779 JF - Cell death & disease JO - Cell Death Dis VL - 10 IS - 10 N2 - Anticancer properties of non-psychoactive cannabinoid cannabidiol (CBD) have been demonstrated on tumors of different histogenesis. Different molecular targets for CBD were proposed, including cannabinoid receptors and some plasma membrane ion channels. Here we have shown that cell lines derived from acute lymphoblastic leukemia of T lineage (T-ALL), but not resting healthy T cells, are highly sensitive to CBD treatment. CBD effect does not depend on cannabinoid receptors or plasma membrane Ca2+-permeable channels. Instead, CBD directly targets mitochondria and alters their capacity to handle Ca2+. At lethal concentrations, CBD causes mitochondrial Ca2+ overload, stable mitochondrial transition pore formation and cell death. Our results suggest that CBD is an attractive candidate to be included into chemotherapeutic protocols for T-ALL treatment. SN - 2041-4889 UR - https://www.unboundmedicine.com/medline/citation/31611561/Cannabidiol_directly_targets_mitochondria_and_disturbs_calcium_homeostasis_in_acute_lymphoblastic_leukemia_ L2 - https://doi.org/10.1038/s41419-019-2024-0 DB - PRIME DP - Unbound Medicine ER -