Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties
Plumbagin is a plant-derived naphthoquinone that is widely used in traditional Asian medicine due to its anti-inflammatory and anti-microbial properties. Additionally, plumbagin is cytotoxic for cancer cells due to its ability to trigger reactive oxygen species (ROS) formation and subsequent apoptos...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2779 |
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| author | Sevinj Sultanli Soni Ghumnani Richa Ashma Katharina F. Kubatzky |
| author_facet | Sevinj Sultanli Soni Ghumnani Richa Ashma Katharina F. Kubatzky |
| author_sort | Sevinj Sultanli |
| collection | DOAJ |
| description | Plumbagin is a plant-derived naphthoquinone that is widely used in traditional Asian medicine due to its anti-inflammatory and anti-microbial properties. Additionally, plumbagin is cytotoxic for cancer cells due to its ability to trigger reactive oxygen species (ROS) formation and subsequent apoptosis. Since it was reported that plumbagin may inhibit the differentiation of bone resorbing osteoclasts in cancer-related models, we wanted to elucidate whether plumbagin interferes with cytokine-induced osteoclastogenesis. Using C57BL/6 mice, we unexpectedly found that plumbagin treatment enhanced osteoclast formation and that this effect was most pronounced when cells were pre-treated for 24 h with plumbagin before subsequent M-CSF/RANKL stimulation. Plumbagin caused a fast induction of NFATc1 signalling and mTOR-dependent activation of p70S6 kinase which resulted in the initiation of protein translation. In line with this finding, we observed an increase in RANK surface expression after Plumbagin stimulation that enhanced the responsiveness for subsequent RANKL treatment. However, in Balb/c mice and Balb/c-derived RAW264.7 macrophages, these findings could not be corroborated and osteoclastogenesis was inhibited. Our results suggest that the effects of plumbagin depend on the model system used and can therefore either trigger or inhibit osteoclast formation. |
| first_indexed | 2024-03-10T13:24:30Z |
| format | Article |
| id | doaj.art-bbef1909d1dd4b79996a7fa861571f33 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:24:30Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bbef1909d1dd4b79996a7fa861571f332023-11-21T09:49:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01225277910.3390/ijms22052779Plumbagin, a Biomolecule with (Anti)Osteoclastic PropertiesSevinj Sultanli0Soni Ghumnani1Richa Ashma2Katharina F. Kubatzky3Zentrum für Infektiologie, Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, GermanyDepartment of Zoology, Savitribai Phule Pune University, Pune 411007, IndiaDepartment of Zoology, Savitribai Phule Pune University, Pune 411007, IndiaZentrum für Infektiologie, Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, GermanyPlumbagin is a plant-derived naphthoquinone that is widely used in traditional Asian medicine due to its anti-inflammatory and anti-microbial properties. Additionally, plumbagin is cytotoxic for cancer cells due to its ability to trigger reactive oxygen species (ROS) formation and subsequent apoptosis. Since it was reported that plumbagin may inhibit the differentiation of bone resorbing osteoclasts in cancer-related models, we wanted to elucidate whether plumbagin interferes with cytokine-induced osteoclastogenesis. Using C57BL/6 mice, we unexpectedly found that plumbagin treatment enhanced osteoclast formation and that this effect was most pronounced when cells were pre-treated for 24 h with plumbagin before subsequent M-CSF/RANKL stimulation. Plumbagin caused a fast induction of NFATc1 signalling and mTOR-dependent activation of p70S6 kinase which resulted in the initiation of protein translation. In line with this finding, we observed an increase in RANK surface expression after Plumbagin stimulation that enhanced the responsiveness for subsequent RANKL treatment. However, in Balb/c mice and Balb/c-derived RAW264.7 macrophages, these findings could not be corroborated and osteoclastogenesis was inhibited. Our results suggest that the effects of plumbagin depend on the model system used and can therefore either trigger or inhibit osteoclast formation.https://www.mdpi.com/1422-0067/22/5/2779osteoclastplumbaginmTORtranslationROSphytotherapy |
| spellingShingle | Sevinj Sultanli Soni Ghumnani Richa Ashma Katharina F. Kubatzky Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties International Journal of Molecular Sciences osteoclast plumbagin mTOR translation ROS phytotherapy |
| title | Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties |
| title_full | Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties |
| title_fullStr | Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties |
| title_full_unstemmed | Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties |
| title_short | Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties |
| title_sort | plumbagin a biomolecule with anti osteoclastic properties |
| topic | osteoclast plumbagin mTOR translation ROS phytotherapy |
| url | https://www.mdpi.com/1422-0067/22/5/2779 |
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