Abstract
BackgroundThe marine environment is a rich source of bioactive natural products. Many of the marine bioactive compounds have been derived successfully from molluscs. Euchelus asper is a marine mollusc which is commonly found in the intertidal rocky regions of the Mumbai coast. The present study was focused on evaluating the anti-angiogenic and anti- proliferative activities of methanolic extract of Euchelus asper (EAME).MethodsThe anti-angiogenic activity of EAME (50–800 μg/mL) was assessed by chick chorio-allantoic membrane (CAM) model wherein multiple parameters in the CAM blood vessels were analysed through morphometric and histological investigations. In vitro testing of EAME (5–20 μg/mL) included its cytotoxicity against three different cancer cell lines, its effect on cell proliferation by wound healing assay as well as their relevant molecular mechanisms. Statistical analysis was carried out by two-tailed student’s t test for two unpaired groups.ResultsAnalysis of CAM revealed that the extract is effective in reducing the branching points of the 1st order blood vessels or capillaries of CAM. Histological analysis of CAM showed significant decrease in capillary plexus and compartmentalization along with increase in mesodermal blood vessels, thus establishing its anti-angiogenicity. Further, EAME exhibited moderate but significant cytotoxicity against A549 non-small cell lung carcinoma cell line. We also demonstrated that the cytotoxicity of EAME in A549 was associated with its apoptotic activity by subG1 phase arrest. Lastly, EAME significantly reduced A549 proliferation by reducing the expression of Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9).ConclusionOverall, our study suggested that EAME has potential to inhibit tumour angiogenic and proliferative activity and may be a potential source for development of new anti-cancer pharmaceuticals.
Highlights
The marine environment is a rich source of bioactive natural products
To further verify whether EAME inhibited the migration of A549 cells, we investigated the regulatory effect of EAME on MMP-2 and Matrix metalloproteinase-9 (MMP-9) that are the key players in cell migration
We have explored the cytotoxic potential of E. asper methanolic extract against three solid tumour cell lines and it was observed that EAME possesses moderate cytotoxicity against A549 cell line
Summary
Many of the marine bioactive compounds have been derived successfully from molluscs. Euchelus asper is a marine mollusc which is commonly found in the intertidal rocky regions of the Mumbai coast. The present study was focused on evaluating the anti-angiogenic and anti- proliferative activities of methanolic extract of Euchelus asper (EAME). Angiogenesis is a physiological process involving growth of nascent blood vessels from the pre-existing vasculature. It is a complex process, regulated by the balance between pro- and anti-angiogenic factors. Interference in regulation of angiogenesis leading to excessive blood supply is associated with diabetic retinopathy, inflammatory diseases as well as cancer growth [1]. Extensive efforts have been taken to target angiogenesis for cancer therapy. It is becoming alarmingly clear that available anti-angiogenic mono-therapies are not meeting their
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