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D,L-Methadone causes leukemic cell apoptosis via an OPRM1-triggered increase in IP3R-mediated ER Ca²⁺ release and decrease in Ca²⁺ efflux, elevating [Ca²⁺]_i.

ABSTRACT: The search continues for improved therapy for acute lymphoblastic leukemia (aLL), the most common malignancy in children. Recently, D,L-methadone was put forth as sensitizer for aLL chemotherapy. However, the specific target of D,L-methadone in leukemic cells and the mechanism by which it induces leukemic cell apoptosis remain to be defined. Here, we demonstrate that D,L-methadone induces leukemic cell apoptosis through activation of the mu1 subtype of opioid receptors (OPRM1). D,L-Methadone evokes IP3R-mediated ER Ca²⁺ release that is inhibited by OPRM1 loss. In addition, the rate of Ca²⁺ extrusion following D,L-methadone treatment is reduced, but is accelerated by loss of OPRM1. These D,L-methadone effects cause a lethal rise in [Ca²⁺]_i that is

SUBMITTER: Lee J

PROVIDER: S-EPMC7806773 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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D,L-Methadone causes leukemic cell apoptosis via an OPRM1-triggered increase in IP3R-mediated ER Ca²⁺ release and decrease in Ca²⁺ efflux, elevating [Ca²⁺]_i.

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

D,L-Methadone causes leukemic cell apoptosis via an OPRM1-triggered increase in IP3R-mediated ER Ca2+ release and decrease in Ca2+ efflux, elevating [Ca2+]i.

OmicsDI is part of the ELIXIR infrastructure

Tweets

D,L-Methadone causes leukemic cell apoptosis via an OPRM1-triggered increase in IP3R-mediated ER Ca²⁺ release and decrease in Ca²⁺ efflux, elevating [Ca²⁺]_i.