Manzamine-A alters in vitro calvarial osteoblast function
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 vi...
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my.um.eprints.408492023-09-26T03:46:28Z http://eprints.um.edu.my/40849/ Manzamine-A alters in vitro calvarial osteoblast function Hardy, Samantha Choo, Yeun Mun Hamann, Mark Cray, James QD Chemistry 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. MDPI 2022-10 Article PeerReviewed 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 https://doi.org/10.3390/md20100647 <https://doi.org/10.3390/md20100647>. 10.3390/md20100647 |
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QD Chemistry Hardy, Samantha Choo, Yeun Mun Hamann, Mark Cray, James Manzamine-A alters in vitro calvarial osteoblast function |
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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. |
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Article |
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Hardy, Samantha Choo, Yeun Mun Hamann, Mark Cray, James |
author_facet |
Hardy, Samantha Choo, Yeun Mun Hamann, Mark Cray, James |
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Hardy, Samantha |
title |
Manzamine-A alters in vitro calvarial osteoblast function |
title_short |
Manzamine-A alters in vitro calvarial osteoblast function |
title_full |
Manzamine-A alters in vitro calvarial osteoblast function |
title_fullStr |
Manzamine-A alters in vitro calvarial osteoblast function |
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Manzamine-A alters in vitro calvarial osteoblast function |
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manzamine-a alters in vitro calvarial osteoblast function |
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MDPI |
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2022 |
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http://eprints.um.edu.my/40849/ |
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13.211869 |