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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Main Authors: Hardy, Samantha, Choo, Yeun Mun, Hamann, Mark, Cray, James
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Published: MDPI 2022
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Online Access:http://eprints.um.edu.my/40849/
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spelling 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
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic QD Chemistry
spellingShingle QD Chemistry
Hardy, Samantha
Choo, Yeun Mun
Hamann, Mark
Cray, James
Manzamine-A alters in vitro calvarial osteoblast function
description 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.
format Article
author Hardy, Samantha
Choo, Yeun Mun
Hamann, Mark
Cray, James
author_facet Hardy, Samantha
Choo, Yeun Mun
Hamann, Mark
Cray, James
author_sort 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
title_full_unstemmed Manzamine-A alters in vitro calvarial osteoblast function
title_sort manzamine-a alters in vitro calvarial osteoblast function
publisher MDPI
publishDate 2022
url http://eprints.um.edu.my/40849/
_version_ 1781704533452259328
score 13.211869