In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A
BACKGROUND: Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo...
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| Format: | Article |
| Language: | en |
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Public Library of Science
2012
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| Online Access: | http://eprints.um.edu.my/3313/1/4.pdf http://eprints.um.edu.my/3313/ https://doi.org/10.1371/journal.pone.0038103 |
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| author | Lai, Siew Li Cheah, Shiau Chuen Wong, Pooi Fong Noor, Suzita Mohd Mustafa, Mohd Rais |
| author_facet | Lai, Siew Li Cheah, Shiau Chuen Wong, Pooi Fong Noor, Suzita Mohd Mustafa, Mohd Rais |
| author_sort | Lai, Siew Li |
| building | UM Library |
| collection | Institutional Repository |
| content_provider | Universiti Malaya |
| content_source | UM Research Repository |
| continent | Asia |
| country | Malaysia |
| description | BACKGROUND:
Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays.
METHODOLOGY/PRINCIPAL FINDINGS:
PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91±0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos.
CONCLUSIONS/SIGNIFICANCE:
Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy. |
| format | Article |
| id | my.um.eprints-3313 |
| institution | Universiti Malaya |
| language | en |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | eprints |
| spelling | my.um.eprints-33132019-11-29T05:04:25Z http://eprints.um.edu.my/3313/ In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A Lai, Siew Li Cheah, Shiau Chuen Wong, Pooi Fong Noor, Suzita Mohd Mustafa, Mohd Rais R Medicine BACKGROUND: Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays. METHODOLOGY/PRINCIPAL FINDINGS: PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91±0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos. CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy. Public Library of Science 2012-05 Article PeerReviewed application/pdf en http://eprints.um.edu.my/3313/1/4.pdf Lai, Siew Li and Cheah, Shiau Chuen and Wong, Pooi Fong and Noor, Suzita Mohd and Mustafa, Mohd Rais (2012) In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A. PLoS ONE, 7 (5). e38103. ISSN 1932-6203, DOI https://doi.org/10.1371/journal.pone.0038103 <https://doi.org/10.1371/journal.pone.0038103>. https://doi.org/10.1371/journal.pone.0038103 doi:10.1371/journal.pone.0038103 |
| spellingShingle | R Medicine Lai, Siew Li Cheah, Shiau Chuen Wong, Pooi Fong Noor, Suzita Mohd Mustafa, Mohd Rais In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A |
| title | In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A |
| title_full | In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A |
| title_fullStr | In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A |
| title_full_unstemmed | In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A |
| title_short | In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A |
| title_sort | in vitro and in vivo anti-angiogenic activities of panduratin a |
| topic | R Medicine |
| url | http://eprints.um.edu.my/3313/1/4.pdf http://eprints.um.edu.my/3313/ https://doi.org/10.1371/journal.pone.0038103 |
| url_provider | http://eprints.um.edu.my/ |