UNASSIGNED: The effectiveness of chemotherapeutic agents often limits their use due to their negative effects on normal cells. Apoptosis regulatory protein ( @entity7136 )-1 functional mimetics (CFMs) belong to a novel class of compounds that possess anti- @entity5 properties with potential utility in @entity0 . In this study, we investigated the growth inhibitory action of CFM-4 and -5 in bone-forming osteoblasts and role of a skeletal regulator, parathyroid hormone (PTH)-related peptide (PTHrP), which is frequently associated with oncologic pathologies. MC3T3E1-clone4 (MC-4) or primary osteoblasts were treated with CFMs. Western blots were performed to determine specific protein expressions. @entity98 , TUNEL assay, @entity5611 / @entity9186 staining, and ApoAlert caspase profiling were used to investigate cell viability and apoptosis of osteoblasts. Immunofluorescence staining was performed to observe intracellular localization of @entity7136 -1. Our studies revealed that CFM-4 and -5 suppressed growths of mature differentiated, but not proliferating, MC-4 cells and PTHrP attenuated this effect. Mechanistically, induction of @entity7136 -1 protein by CFM-4 and -5 was partially decreased by PTHrP. While @entity7136 -1 increased by CFM-4 or -5 correlated with activated caspase-3, PTHrP remarkably blocked caspase-3 activation. PTHrP also influenced translocation of CFM-induced @entity7136 -1 from the nucleus to the cytoplasm. Our data identify a new function of PTHrP in maintaining osteoblast homeostasis in chemotherapy and define a role of @entity7136 -1 in this process. The crosstalk of PTHrP and CFM-4 and -5 signaling highlights the importance of CFMs as potential anti- @entity5 therapeutics in @entity0 which adversely affect bone.

PTHrP attenuates osteoblast cell death and apoptosis induced by a novel class of anti- XXXX agents.

@entity0 :: ('MESH:D001943', 'Disease') :: ['breast and other cancers'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity5611 :: ('MESH:D004996', 'Chemical') :: ['ethidium bromide'] @entity98 :: ('CHEBI:53233', 'Chemical') :: ['MTT'] @entity7136 :: ('7962', 'Species') :: ['CARP'] @entity9186 :: ('MESH:D000165', 'Chemical') :: ['acridine orange']
@entity5 :: (MESH:D009369,Disease) :: ['cancer']
