Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2020 | Colon Cancer | Research article

Differential inhibition of gelatinase activity in human colon adenocarcinoma cells by Aloe vera and Aloe arborescens extracts

Authors: Ana Lima, Paula Batista-Santos, Eduarda Veríssimo, Patrícia Rebelo, Ricardo Boavida Ferreira

Published in: BMC Complementary Medicine and Therapies | Issue 1/2020

Abstract

Background

Aloe’s reported bioactivities (anticancer, anti-inflammatory and wound healing) suggest they might inhibit a subgroup of matrix metalloproteinases (MMPs) called gelatinases (MMP-2 and MMP-9). The goal of the present study was to compare the MMP inhibitory potential of two Aloe species, A. vera and A. arborescens.

Methods

Different types of extraction were tested and specific bioactive compounds were quantified. Cancer cell invasion inhibitory activities were measured in vitro using the wound healing assay in human colon cancer cells (HT29). Effects on gelatinase activities were further assessed by dye-quenched gelatin and gelatin zymography.

Results

Different types of extraction yielded significantly different levels of bioactivities and of bioactive compounds, which might be due to a greater amount of extractable bioactive compounds such as anthraquinones. Both A. arborescens and A. vera have potential as inhibitory agents in cancer cell proliferation via MMP-9 and MMP-2 enzymatic activity inhibition, being able to reduce colon cancer cell proliferation and migration but A. arborescens showed to be a more effective inhibitor of cancer cell migration than A. vera.

Conclusion

This work opens novel perspectives on the mode of action of Aloe species in cancer cell migration and may provide clues as to why there are so many conflicting results on Aloe’s activities.

Foster M, Hunter D, Samman S. Evaluation of the Nutritional and Metabolic Effects of Aloe vera. In: Benzie IF, Wachtel-Galor S, editors. Herbal medicine: biomolecular and clinical aspects. New York: CRC Press; 2011. p. 37–9.CrossRef

Orta G. Colóquios dos Simples e Drogas da India. 2nd ed. Lisboa: Imprensa nacional; 1895.

Hamman JH. Composition and applications of Aloe vera leaf gel. Molecules. 2008;13:1599–616 https://doi.org/10.3390/molecules13081599.PubMedPubMedCentralCrossRef

Kumar R, Singha AK, Guptaa A, Bishayeeb A, Pandeya AK. Therapeutic potential of Aloe vera—a miracle gift of nature. Phytomedicine. 2019;60:152996 https://doi.org/10.1016/j.phymed.2019.152996.PubMedCrossRef

Singab ANB, El-Hefnawy HM, Esmat A, Gad HA, Nazeam JA. A systemic review on Aloe arborescens pharmacological profile: biological activities and pilot clinical trials. Phytother Res. 2015;29:1858–67 https://doi.org/10.1002/ptr.5483.PubMedCrossRef

Salehi B, Albayrak S, Antolak H, Kregiel D, Pawlikowska E, Sharifi-Rad M, Uprety Y, Tsouh Fokou PV, Yousef Z, Zakaria ZA, Varoni EM, Sharopov F, Martins N, Iriti M, Sharifi-Rad J. Aloe genus plants: from farm to food applications and Phytopharmacotherapy. Int J Mol Sci. 2018;19:2843 https://doi.org/10.3390/ijms19092843.PubMedCentralCrossRef

Gupta VK, Malhotra S. Pharmacological attribute of Aloe vera: revalidation through experimental and clinical studies. AYU. 2012;33(2):193–6 https://doi.org/10.4103/0974-8520.105237.PubMedPubMedCentralCrossRef

Sahu PK, Giri DD, Singh R, Pandey P, Gupta S, Shrivastava AK, Kumar A, Pandey KD. Therapeutic and medicinal uses of Aloe vera: a review. Pharmacol Pharm. 2013;4:599–610 https://doi.org/10.4236/pp.2013.48086.CrossRef

Bhalang K, Tompkins K. Polysaccharides from Aloe vera and Oral ulcerations. In: Ramawat KG, Merillon JM, editors. Polysaccharides: bioactivity and biotechnology. Switzerland: Springer International; 2015. p. 2137–50.CrossRef

10.

Yagi A, Byung PY. Immune modulation of Aloe vera: Acemannan and gut microbiota modulator. J GHR. 2015;4:1707–21 https://doi.org/10.17554/j.issn.2224-3992.2015.04.525.

11.

Amoo SO, Aremu AO, Van Staden J. Unraveling the medicinal potential of south African Aloe species. J Ethnopharmacol. 2014;153:19–41 https://doi.org/10.1016/j.jep.2014.01.036.PubMedCrossRef

12.

Sánchez M, González-Burgos E, Iglesias I, Gómez-Serranillos MP. Pharmacological update properties of Aloe Vera and its major active constituents. Molecules. 2020;25(6):1324 https://doi.org/10.3390/molecules25061324.PubMedCentralCrossRef

13.

Grace OM, Buerki S, Symonds MR, Forest F, Van Wyk AE, Smith GF, Klopper RR, Bjorå CS, Neale S, Demissew S, Simmonds MSJ, Rønsted N. Evolutionary history and leaf succulence as explanations for medicinal use in aloes and the global popularity of Aloe vera. BMC Evol Biol. 2015;15:29 https://doi.org/10.1186/s12862-015-0291-7.PubMedPubMedCentralCrossRef

14.

Guo X, Mei N. Aloe Vera: a review of toxicity and adverse clinical effects. J Environ Sci Heal C. 2016;34:77–96 https://doi.org/10.1080/10590501.2016.1166826.CrossRef

15.

Mahomoodally MF. Traditional medicines in Africa: an appraisal of ten potent African medicinal plants. Evid-Based Compl Alt. 2013:1–14 https://doi.org/10.1155/2013/617459.

16.

Femenia A, Sánchez ES, Simal S, Rosselló C. Compositional features of polysaccharides from Aloe vera (Aloe barbadensis miller) plant tissues. Carbohyd Polym. 1999;39:109–17.CrossRef

17.

Telefo PB, Moundipa PF, Tchouanguep FM. Oestrogenicity and effect on hepatic metabolism of the aqueous extract of the leaf mixture of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus and Justicia insularis. Fitoterapia. 2002;73:472–8 https://doi.org/10.1016/S0367-326X(02)00177-6.PubMedCrossRef

18.

Arnold CN, Goel A, Blum HE, Richard BC. Molecular pathogenesis of colorectal cancer. Cancer. 2005;104:2035–47 https://doi.org/10.1002/cncr.21462.PubMedCrossRef

19.

Kryczka J, Stasiak M, Dziki L, Mik M, Dziki A, Cierniewski CS. Matrix metalloproteinase-2 cleavage of the β1 integrin ectodomain facilitates colon cancer cell motility. J Biol Chem. 2002;287:36556–66 https://doi.org/10.1074/jbc.M112.384909.CrossRef

20.

Oliveira I, Nunes A, Lima A, Borralho P, Rodrigues C, Ferreira RB, Ribeiro AC. New Lectins from Mediterranean Flora. Activity against HT29 Colon Cancer cells. Int J Mol Sci. 2019;20:3059.PubMedCentralCrossRef

21.

Kyriakides T, Wulsin D, Eleni D, Skokos A, Fleckman P, Pirrone J, Shipley M, Senior RM, Bornstein P. Mice that lack matrix metalloproteinase-9 display delayed wound healing associated with delayed reepithelization and disordered collagen fibrillogenesis. Matrix Biol. 2009;28:65–73 https://doi.org/10.1016/j.matbio.2009.01.001.PubMedPubMedCentralCrossRef

22.

Reiss MJ, Han YP, Garcia E, Goldberg M, Hong YK, Garner WL. Matrix Metalloproteinase-9 delays wound healing in a murine wound model. Surgery. 2010;147:295–308 https://doi.org/10.1016/j.surg.2009.10.016.PubMedCrossRef

23.

Vijayalakshmi D, Dhandapani R, Jayaveni S, Jithendra PS, Rose C, Mandal AB. In vitro anti inflammatory activity of Aloe vera by down regulation of MMP-9 in peripheral blood mononuclear cells. J Ethnopharmacol. 2012;141:542–6 https://doi.org/10.1016/j.jep.2012.02.040.PubMedCrossRef

24.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.PubMedCrossRef

25.

Charmont S, Jamet E, Pont-Lezica R, Canut H. Proteomic analysis of secreted proteins from Arabidopsis thaliana seedlings: improved recovery following removal of phenolic compounds. Phytochemistry. 2005;6:453–61.CrossRef

26.

Ainsworth EA, Gillespie KM. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin–Ciocalteau reagent. Nat Protoc. 2007;2:875–7.PubMedCrossRef

27.

Shabbir M, Khan MR, Saeed N. Assessment of phytochemicals, antioxidant, anti-lipid peroxidation and anti-hemolytic activity of extract and various fractions of Maytenus royleanus leaves. BMC Complement Altern Med. 2013;13:143–56 https://doi.org/10.1186/1472-6882-13-143.PubMedPubMedCentralCrossRef

28.

Dallies N, Francois J, Paquet V. A new method for quantitative determination of polysaccharides in the yeast cell wall. Application to the cell wall defective mutants of Saccharomyces cerevisiae. Yeast. 1998;14:1297–306.PubMedCrossRef

29.

Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 1987;47:936–42.PubMed

30.

Lima AIG, Mota J, Monteiro SAVS, Ferreira RMSB. Legume seeds and colorectal cancer revisited: Protease inhibitors reuce MMP-9 activity and colon cancer cell migration. Food Chem. 2016;197(Part A):30–8. https://doi.org/10.1016/j.foodchem.2015.10.063.PubMedCrossRef

31.

López A, Tangil MS, Vega-Orellana O, Ramírez AS, Rico M. Phenolic constituents, antioxidant and preliminary antimycoplasmic activities of leaf skin and flowers of Aloe vera (L.) Burm. F. (syn. A. barbadensis mill.) from the Canary Islands (Spain). Molecules. 2013;18:4942–54. https://doi.org/10.3390/molecules18054942.PubMedPubMedCentralCrossRef

32.

Kim HS, Luo L, Pflugfelder SC, Li DQ. Doxycycline inhibits TGF-β1–induced MMP-9 via Smad and MAPK pathways in human corneal epithelial cells. Invest Ophth Vis Sci. 2005;46:840–8. https://doi.org/10.1167/iovs.04-0929.CrossRef

33.

Dagne E, Bisrat D, Viljoen A, Van Wyk BE. Chemistry of Aloe species. Curr Org Chem. 2000;4:1055–78.CrossRef

34.

Choi S, Chung MH. A review on the relationship between Aloe vera components and their biologic effects. Semin Integr Med. 2003;1:53–62.CrossRef

35.

Ni Y, Tizard IR. Analytical methodology: the gel-analysis of aloe pulp and its derivatives. In: Reynolds T, editor. Aloe: the genus Aloe. Boca Raton: CRC Press; 2004. p. 111–26.

36.

Park MK, Park JH, Kim NY, Shin YG, Choi YS, Lee JG, Kim KH, Lee SK. Analysis of 13 phenolic compounds in Aloe species by high performance liquid chromatography. Phytochem Anal. 1998;9:186–91.CrossRef

37.

Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79:727–47. https://doi.org/10.1093/ajcn/79.5.727.PubMedCrossRef

38.

Harlev E, Nevo E, Lansky EP, Ofir R, Bishayee A. Anticancer potential of aloes: antioxidant, antiproliferative, and immunostimulatory attributes. Planta Med. 2012;78:843–52 https://doi.org/10.1055/s-0031-1298453.PubMedCrossRef

39.

Wang Z, Wang Y, Huang Z, Zhong S, Wu Y, Yu L. Study on antitumor effect and mechanism of Aloe polysaccharides. J Chinese Med Mater. 2001;24:350–3.

40.

Bourguet E, Alix AJP, Moroy G, Sapi J, Hornebeck W. Pharmacomodulation of broad spectrum matrix metalloproteinase inhibitors towards regulation of gelatinases. In: Sharma R, editor. Enzyme Inhibition and Bioapplications: IntechOpen; 2012. p. 57–63. https://doi.org/10.5772/35412.

41.

Hidalgo M, Eckhardt SG. Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer I. 2001;93:178–93. https://doi.org/10.1093/jnci/93.3.178.CrossRef

42.

Eshun K, He Q. Aloe vera: a valuable ingredient for the food, pharmaceutical and cosmetic industries—a review. Crit Rev Food Sci. 2004;44:91–6. https://doi.org/10.1080/10408690490424694.CrossRef

43.

Lawrence R, Tripathi P, Jeyakumar E. Isolation, purification and evaluation of antibacterial agents from Aloe vera. Braz J Microbiol. 2009;40:906–15. https://doi.org/10.1590/S1517-83822009000400023.PubMedPubMedCentralCrossRef

44.

Lissoni P, Rovelli F, Brivio F, Zago R, Colciago M, Messina G, Mora A, Porro G. A randomized study of chemotherapy versus biochemotherapy with chemotherapy plus Aloe arborescens in patients with metastatic cancer. In Vivo. 2009;23:171–5.PubMed

45.

Yarrow JC, Perlman ZE, Westwood NJ. Mitchison TJ. A high-throughput cell migration assay using scratch wound healing, a comparison of image-based readout methods. BMC Biotechnol. 2004;4:21–30. https://doi.org/10.1186/1472-6750-4-21.PubMedPubMedCentralCrossRef

46.

Di Luccia B, Manzo N, Vivo M, Galano E, Amoresano A, Crescenzi E, Pollice A, Tudisco R, Infascelli F, Calabrò V. A biochemical and cellular approach to explore the antiproliferative and prodifferentiative activity of Aloe arborescens leaf extract. Phytother Res. 2003;27:1819–28. https://doi.org/10.1002/ptr.4939.CrossRef

47.

Direito R, Lima A, Mota J, Ferreira RB, Rocha J, Bronze MR, Sepodes B, Figueira ME. Dyospiros kaki presents anti-inflammatory and anticancer activity with concomitant MMP-9 inhibition. J Nutr Biochem. 2017;46:100–8. https://doi.org/10.1016/j.jnutbio.2017.03.002.PubMedCrossRef

48.

Lima A, Oliveira J, Saúde F, Mota J, Ferreira RB. Proteins in soy might have a higher role in cancer prevention than previously expected: soybean protein fractions are more effective MMP-9 inhibitors than non-protein fractions, even in cooked seeds. Nutrients. 2017;9:201. https://doi.org/10.3390/nu9030201.PubMedCentralCrossRef

49.

Froldi G, Baronchelli F, Marin E, Grison M. Antiglycation activity and HT-29 cellular uptake of Aloe-Emodin, Aloin, and Aloe arborescens leaf extracts. Molecules. 2019;24:2128. https://doi.org/10.3390/molecules24112128.PubMedCentralCrossRef

50.

Moss LAS, Jensen-Taubman S, Stetler-Stevenson WG. Matrix metalloproteinases: changing roles in tumor progression and metastasis. Am J Pathol. 2012;181:1895–9 https://doi.org/10.1016/j.ajpath.2012.08.044.CrossRef

51.

Herszényi L, Hritz I, Lakatos G, Varga MZ, Tulassay Z. The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. Int J Mol Sci. 2012;13:13240–63 https://doi.org/10.3390/ijms131013240.PubMedPubMedCentralCrossRef

52.

Murthy NS, Mukherjee S, Ray G, Ray A. Dietary factors and cancer chemoprevention: an overview of obesity-related malignancies. J Postgrad Med. 2009;55:45–54 https://doi.org/10.4103/0022-3859.43549.PubMedCrossRef

Title: Differential inhibition of gelatinase activity in human colon adenocarcinoma cells by Aloe vera and Aloe arborescens extracts
Authors: Ana Lima
Paula Batista-Santos
Eduarda Veríssimo
Patrícia Rebelo
Ricardo Boavida Ferreira
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Colon Cancer
Colon Cancer
Published in: BMC Complementary Medicine and Therapies / Issue 1/2020
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-020-03134-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Differential inhibition of gelatinase activity in human colon adenocarcinoma cells by Aloe vera and Aloe arborescens extracts

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2020

Do women who consult with naturopaths or herbalists have a healthy lifestyle?: a secondary analysis of the Australian longitudinal study on women’s health

Traditional Uyghur medicine Quercus infectoria galls water extract triggers apoptosis and autophagic cell death in colorectal cancer cells

Ethnobotanical survey on plants used in the treatment of candidiasis in traditional markets of southern Benin

Evaluation of peptide-rich root extracts of Calliandria portoriscensis (Jacq.) Benth (Mimosaceae) for in vitro antimicrobial activity and brine shrimp lethality

Effectiveness and cerebral responses of multi-points acupuncture for primary insomnia: a preliminary randomized clinical trial and fMRI study

Dasatinib reverses drug resistance by downregulating MDR1 and Survivin in Burkitt lymphoma cells