Manzamine-A alters in vitro calvarial osteoblast function

Hardy, Samantha and Choo, Yeun Mun and Hamann, Mark and Cray, James (2022) Manzamine-A alters in vitro calvarial osteoblast function. Marine Drugs, 20 (10). ISSN 1660-3397, DOI

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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 affect bone. We hypothesize that Manzamine-A, through SIX1, alters bone cell activity. Here, we assessed the effects of Manzamine-A on cells that are responsible for the generation of bone, pre-osteoblasts and osteoblasts. PCR, qrtPCR, MTS cell viability, Caspase 3/7, and functional assays were used to test the effects of Manzamine-A on these cells. Our data suggests Six1 is highly expressed in osteoblasts and their progenitors. Further, osteoblast progenitors and osteoblasts exhibit great sensitivity to Manzamine-A treatment exhibited by a significant decrease in cell viability, increase in cellular apoptosis, and decrease in alkaline phosphatase activity. In silico binding experiment showed that manzamine A potential as an inhibitor of cell proliferation and survival proteins, i.e., I kappa b, JAK2, AKT, PKC, FAK, and Bcl-2. Overall, our data suggests Manzamine-A may have great effects on bone health overall and may disrupt skeletal development, homeostasis, and repair.

Item Type: Article
Funders: Ohio State College of Medicine
Uncontrolled Keywords: Manzamine; Bone; Osteoblast; Six1; Osteogenesis
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Science
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 26 Sep 2023 03:46
Last Modified: 26 Sep 2023 03:46

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