Methanolic Extract of Euchelus Asper Exhibits In-ovo Anti-angiogenic and in Vitro Anti-proliferative Activities

Overview

Journal Biol Res

Specialty Biology

Date 2017 Dec 14

PMID 29233192

Citations 6

Authors

Sweta Agrawal

Sachin Chaugule

Shashank More

Gargi Rane

Madhavi Indap

Affiliations

Soon will be listed here.

Abstract

Background: The 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).

Methods: The 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.

Results: Analysis 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).

Conclusion: Overall, 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.

Citing Articles

Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment Design.

Zheng N, Li X, Zhou N, Luo L Mar Drugs. 2025; 23(1).

PMID: 39852526 PMC: 11767183. DOI: 10.3390/md23010024.

In Silico Analysis of USP7 Inhibitors Based on Building QSAR Models and Fragment Design for Screening Marine Compound Libraries.

Tan H, Li C, Lai T, Luo L Mar Drugs. 2024; 22(1).

PMID: 38276639 PMC: 10817464. DOI: 10.3390/md22010001.

Lidocaine induces epithelial‑mesenchymal transition and aggravates cancer behaviors in non‑small cell lung cancer A549 cells.

Hsieh W, Liao S, Chan S, Hou J, Wu S, Ho B Oncol Lett. 2023; 26(2):346.

PMID: 37427341 PMC: 10326810. DOI: 10.3892/ol.2023.13932.

Natural Products with Activity against Lung Cancer: A Review Focusing on the Tumor Microenvironment.

Yang Y, Li N, Wang T, Di L Int J Mol Sci. 2021; 22(19).

PMID: 34639167 PMC: 8509218. DOI: 10.3390/ijms221910827.

Molluscan Compounds Provide Drug Leads for the Treatment and Prevention of Respiratory Disease.

Summer K, Browne J, Liu L, Benkendorff K Mar Drugs. 2020; 18(11).

PMID: 33228163 PMC: 7699502. DOI: 10.3390/md18110570.

References

Garcia-Caballero M, Canedo L, Fernandez-Medarde A, Medina M, Quesada A . The marine fungal metabolite, AD0157, inhibits angiogenesis by targeting the Akt signaling pathway. Mar Drugs. 2014; 12(1):279-99. PMC: 3917274. DOI: 10.3390/md12010279. View

Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D . New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 1990; 82(13):1107-12. DOI: 10.1093/jnci/82.13.1107. View

Baharara J, Amini E, Mousavi M . The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star. Rep Biochem Mol Biol. 2016; 3(2):68-75. PMC: 4757044. View

Antonova O, Dolashka P, Toncheva D, Rammensee H, Floetenmeyer M, Stevanovic S . In vitro antiproliferative effect of Helix aspersa hemocyanin on multiple malignant cell lines. Z Naturforsch C J Biosci. 2014; 69(7-8):325-34. DOI: 10.5560/znc.2013-0148. View

Toth M, Fridman R . Assessment of Gelatinases (MMP-2 and MMP-9 by Gelatin Zymography. Methods Mol Med. 2011; 57:163-74. PMC: 3845455. DOI: 10.1385/1-59259-136-1:163. View

Melkonian G, Munoz N, Chung J, Tong C, Marr R, Talbot P . Capillary plexus development in the day five to day six chick chorioallantoic membrane is inhibited by cytochalasin D and suramin. J Exp Zool. 2002; 292(3):241-54. DOI: 10.1002/jez.10014. View

Chen S, Chien Y, Pan C, Sheu J, Chen C, Wu C . Inhibitory effect of dihydroaustrasulfone alcohol on the migration of human non-small cell lung carcinoma A549 cells and the antitumor effect on a Lewis lung carcinoma-bearing tumor model in C57BL/6J mice. Mar Drugs. 2014; 12(1):196-213. PMC: 3917270. DOI: 10.3390/md12010196. View

Manjunathan R, Ragunathan M . In ovo administration of human recombinant leptin shows dose dependent angiogenic effect on chicken chorioallantoic membrane. Biol Res. 2015; 48:29. PMC: 4470073. DOI: 10.1186/s40659-015-0021-z. View

Sawadogo W, Schumacher M, Teiten M, Cerella C, Dicato M, Diederich M . A survey of marine natural compounds and their derivatives with anti-cancer activity reported in 2011. Molecules. 2013; 18(4):3641-73. PMC: 6270579. DOI: 10.3390/molecules18043641. View

10.

Makin G, Hickman J . Apoptosis and cancer chemotherapy. Cell Tissue Res. 2000; 301(1):143-52. DOI: 10.1007/s004419900160. View

11.

Bergers G, Hanahan D . Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer. 2008; 8(8):592-603. PMC: 2874834. DOI: 10.1038/nrc2442. View

12.

Ellis L, Hicklin D . VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008; 8(8):579-91. DOI: 10.1038/nrc2403. View

13.

Kalimuthu S, Se-Kwon K . Cell survival and apoptosis signaling as therapeutic target for cancer: marine bioactive compounds. Int J Mol Sci. 2013; 14(2):2334-54. PMC: 3587990. DOI: 10.3390/ijms14022334. View

14.

Webb A, Gao B, Goldsmith Z, Irvine A, Saleh N, Lee R . Inhibition of MMP-2 and MMP-9 decreases cellular migration, and angiogenesis in in vitro models of retinoblastoma. BMC Cancer. 2017; 17(1):434. PMC: 5477686. DOI: 10.1186/s12885-017-3418-y. View

15.

Huang S, Wang C, Yang R, Wu H, Yang S, Cheng Y . Ellagic Acid, the Active Compound of Phyllanthus urinaria, Exerts In Vivo Anti-Angiogenic Effect and Inhibits MMP-2 Activity. Evid Based Complement Alternat Med. 2009; 2011:215035. PMC: 3095481. DOI: 10.1093/ecam/nep207. View

16.

Liang C, Park A, Guan J . In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007; 2(2):329-33. DOI: 10.1038/nprot.2007.30. View

17.

Klein T, Bischoff R . Physiology and pathophysiology of matrix metalloproteases. Amino Acids. 2010; 41(2):271-90. PMC: 3102199. DOI: 10.1007/s00726-010-0689-x. View

18.

Balakrishnan B, Chiplunkar S, Indap M . Methanol Extract of Euchelus asper Prevents Bone Resorption in Ovariectomised Mice Model. J Osteoporos. 2014; 2014:348189. PMC: 4068096. DOI: 10.1155/2014/348189. View

19.

Riccardi C, Nicoletti I . Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc. 2007; 1(3):1458-61. DOI: 10.1038/nprot.2006.238. View

20.

Bae W, Lim H, Kim K, Cho H, Lee S, Jeong C . Apoptosis-Inducing Activity of Marine Sponge Haliclona sp. Extracts Collected from Kosrae in Nonsmall Cell Lung Cancer A549 Cells. Evid Based Complement Alternat Med. 2015; 2015:717959. PMC: 4508479. DOI: 10.1155/2015/717959. View