Department of Biomedical Education and Anatomy, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Chemistry Department, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia.
Mar Drugs. 2022 Oct 19;20(10):647. doi: 10.3390/md20100647.
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., Iκb, 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.
曼扎胺-A 是一种海洋衍生的生物碱，具有抗病毒和抗增殖特性，目前正在研究其在治疗某些病毒（疟疾、疱疹、HIV-1）和癌症（乳腺癌、宫颈癌、结直肠癌）方面的疗效。曼扎胺-A 通过调节 SIX1 基因表达发挥作用，SIX1 基因是颅面发育过程中通过 WNT、NOTCH 和 PI3K/AKT 途径的关键基因。迄今为止，很少有研究关注曼扎胺-A 及其使用如何影响骨骼。我们假设曼扎胺-A 通过 SIX1 改变骨细胞的活性。在这里，我们评估了曼扎胺-A 对负责产生骨骼的细胞（成骨前体细胞和成骨细胞）的影响。PCR、qrtPCR、MTS 细胞活力、Caspase 3/7 和功能测定用于测试曼扎胺-A 对这些细胞的影响。我们的数据表明，SIX1 在成骨细胞及其祖细胞中高度表达。此外，成骨细胞前体细胞和成骨细胞对曼扎胺-A 治疗非常敏感，表现为细胞活力显著降低、细胞凋亡增加和碱性磷酸酶活性降低。计算机结合实验表明，曼扎胺 A 可能是一种抑制细胞增殖和存活蛋白的潜在物质，即 Iκb、JAK2、AKT、PKC、FAK 和 Bcl-2。总的来说，我们的数据表明曼扎胺-A 可能对整体骨骼健康有很大影响，并可能破坏骨骼发育、平衡和修复。
