(482.11) Investigating the effects of the marine drug Manzamine-A related to craniofacial development in vitro

Poster Board Number: C126
Introduction: AAA has separate poster presentation times for odd and even posters.
Odd poster #s – 10:15 am – 11:15 am
Even poster #s – 11:15 am – 12:15 pm

Samantha Hardy (The Ohio State University), Mark Hamann (Medical University of South Carolina), James Cray (The Ohio State University)

Manzamine-A is a marine-derived alkaloid which has anti-viral and anti-proliferative properties and is currently being investigated for its efficacy in the treatment of certain viruses (malaria, herpes, HIV-1) and cancers (breast, cervical, colorectal). Manzamine-A has been found to exert effects via modulation of SIX1 gene expression, a gene critical to craniofacial development via the WNT, NOTCH, and PI3K/AKT pathways. To date little work has focused on Manzamine-A and how its use may effect craniofacial development. We hypothesize that Manzamine-A, through SIX1, alters bone cell activity important to craniofacial skeletal development. As Manzamine-A is a drug that has great potential in a variety of therapeutics, it is critical that we asses potential side effects that this drug could have on both patients and any developmental effects that may occur during use by expectant mothers. We aimed to assess the effects of Manzamine-A on four cell types, pre-osteoblasts, osteoblasts, pre-osteoclasts, and osteoclasts. PCR, qrtPCR, MTS cell viability assays and Caspase 3/7 apoptosis assay were used to test the effects of Manzamine-A on these cells. We also performed alkaline phosphatase (ALP) and Tartrate Resistant Acid Phosphatase (TRAP) assays to test the function of osteoblasts and osteoclasts respectively. To date we have found that Six-1 is highly expressed in osteoblasts and their progenitors. In contrast Six-1 has low expression levels in osteoclasts and their progenitors. Further, osteoblast progenitor cells exhibit great sensitivity to Manzamine-A treatment exhibited by a significant decrease in cell viability, increase in cellular apoptosis, and decrease in ALP activity. Studies are ongoing for osteoclast lineage cells. Overall our preliminary data suggests Manzamine-A may have great effects on bone health overall and may disrupt skeletal development if exposed during pregnancy or postnatal development.