NDLI: AECHL-1, a novel triterpenoid, targets tumor neo-vasculature and impairs the endothelial cell cytoskeleton

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AECHL-1, a novel triterpenoid, targets tumor neo-vasculature and impairs the endothelial cell cytoskeleton

Content Provider	PubMed Central
Author	Dasgupta, Aparajita Sawant, Mithila A. Lavhale, Manish S. Krishnapati, Lakshmi-surekha Surendra, Ghaskadbi Sitasawad, Sandhya L.
Abstract	Tumor angiogenesis is characterized by abnormal vessel morphology leading to erratic and insufficient delivery of chemotherapeutics and oxygen, making the tumor core not only highly hypoxic but also unresponsive toward treatment. Such hypoxic conditions promote tumor aggressiveness, leading to the establishment of metastatic disease. Most anti-angiogenic treatments aim toward the destruction of tumor vasculature, which proves countereffective by further increasing its aggressive nature. Hence, developing drugs which target or regulate these processes might lead to a better delivery of chemotherapeutics resulting in tumor shrinkage. Plant-derived natural compounds having a bioactive ingredient, especially triterpenoids, have been known to possess anticancer properties. AECHL-1, a recently isolated novel triterpenoid with proven anticancer potential, is seemingly noncytotoxic toward HEK 293 and HUVECs. Also, cytotoxicity was absent during in vivo studies involving intraperitoneal injections with 5 µg/kg body weight AECHL-1 on SCID mice. When used at subtoxic doses, it was found to be effective in suppression of neo-vessel formation as demonstrated in the chick chorioallantoic membrane, rat aortic rings, Matrigel plugs and xenograft tumors implanted in SCID mice. Tumor vasculature from AECHL-1-treated mice showed greater mural cell coverage and relatively normalized architecture. Investigations into the molecular mechanisms responsible for these observations revealed an effect on the actin cytoskeleton of stimulated HUVECs as well as the VEGFR2-mediated MAPK pathway. AECHL-1 could effectively distinguish between stimulated and nonstimulated endothelial cells. AECHL-1 could also downregulate HIF-1α expression and VEGF secretion under hypoxic conditions, thus reducing the fears of unnecessarily aggravating tumor metastasis as a result of anti-angiogenic therapy. Results obtained from the aforementioned studies make it clear that though AECHL-1 shows promise in discouraging and pruning neo-vasculature, it may not affect existing vasculature as the doses used for the assays are significantly lower than the ones causing endothelial cell death and has potential to be considered as a candidate for therapeutic drug development.
Related Links	http://dx.doi.org/10.1007/s10456-015-9466-5
Ending Page	299
Page Count	17
Starting Page	283
File Format	PDF
ISSN	09696970
e-ISSN	15737209
Journal	Angiogenesis
Issue Number	3
Volume Number	18
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-07-01
Access Restriction	Open
Rights Holder	Springer Netherlands
Subject Keyword	Clinical Biochemistry Cancer Research Physiology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Clinical Biochemistry Cancer Research

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