posted on 2024-02-22, 03:03authored byTyler Maykovich, Samantha Hardy, Mark T. Hamann, James Cray
Manzamine-A is a marine-derived alkaloid that has demonstrated
antimalarial and antiproliferative properties and is an emerging drug
lead compound as a possible intervention in certain cancers. This
compound has been found to modulate SIX1 gene expression,
a target that is critical for the proliferation and survival of cells
via various developmental pathways. As yet, little research has focused
on manzamine-A and how its use may affect tissue systems including
bone. Here we hypothesized that manzamine-A, through its interaction
with SIX1, would alter precursor cells that give
rise to the bone cell responsible for remodeling: the osteoclast.
We further hypothesized reduced effects in differentiated osteoclasts,
as these cells are generally not mitotic. We interrogated the effects
of manzamine-A on preosteoclasts and osteoclasts. qrtPCR, MTS cell
viability, Caspase 3/7, and TRAP staining were used as a functional
assay. Preosteoclasts show responsiveness to manzamine-A treatment
exhibited by decreases in cell viability and an increase in apoptosis.
Osteoclasts also proved to be affected by manzamine-A but only at
higher concentrations where apoptosis was increased and activation
was reduced. In summary, our presented results suggest manzamine-A
may have significant effects on bone development and health through
multiple cell targets, previously shown in the osteoblast cell lineage,
the cell responsible for mineralized tissue formation, and here in
the osteoclast, the cell responsible for the removal of mineralized
tissue and renewal via precipitation of bone remodeling.