Aplidin (plitidepsin) is a novel anti-myeloma agent with potent anti-resorptive activity mediated by direct effects on osteoclasts.

Article Details

Citation

Copy to clipboard

Delgado-Calle J, Kurihara N, Atkinson EG, Nelson J, Miyagawa K, Galmarini CM, Roodman GD, Bellido T

Aplidin (plitidepsin) is a novel anti-myeloma agent with potent anti-resorptive activity mediated by direct effects on osteoclasts.

Oncotarget. 2019 Apr 12;10(28):2709-2721. doi: 10.18632/oncotarget.26831. eCollection 2019 Apr 12.

PubMed ID

31105871 [ View in PubMed

]

Abstract

Despite recent progress in its treatment, Multiple Myeloma (MM) remains incurable and its associated bone disease persists even after complete remission. Thus, identification of new therapeutic agents that simultaneously suppress MM growth and protect bone is an unmet need. Herein, we examined the effects of Aplidin, a novel anti-cancer marine-derived compound, on MM and bone cells. In vitro, Aplidin potently inhibited MM cell growth and induced apoptosis, effects that were enhanced by dexamethasone (Dex) and bortezomib (Btz). Aplidin modestly reduced osteocyte/osteoblast viability and decreased osteoblast mineralization, effects that were enhanced by Dex and partially prevented by Btz. Further, Aplidin markedly decreased osteoclast precursor numbers and differentiation, and reduced mature osteoclast number and resorption activity. Moreover, Aplidin reduced Dex-induced osteoclast differentiation and further decreased osteoclast number when combined with Btz. Lastly, Aplidin alone, or suboptimal doses of Aplidin combined with Dex or Btz, decreased tumor growth and bone resorption in ex vivo bone organ cultures that reproduce the 3D-organization and the cellular diversity of the MM/bone marrow niche. These results demonstrate that Aplidin has potent anti-myeloma and anti-resorptive properties, and enhances proteasome inhibitors blockade of MM growth and bone destruction.

DrugBank Data that Cites this Article

Drugs

Plitidepsin

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Plitidepsin	Elongation factor 1-alpha 2	Protein	Humans	Unknown	Not Available	Details