Cytotoxicity of bark extracts from Aglaia loheri (Blanco) Merr. (Meliaceae) against human colorectal carcinoma cells (HCT116)
Paper Details
Cytotoxicity of bark extracts from Aglaia loheri (Blanco) Merr. (Meliaceae) against human colorectal carcinoma cells (HCT116)
Abstract
Natural products, plant extracts or plant-derived chemicals have played a promising role in the treatment and prevention of cancer showing considerably less toxicity and lack the side effects of other chemotherapeutic agents. The cytotoxic activity of bark extracts from a Philippine native tree, Aglaia loheri, were tested against human colorectal cancer cell line HCT116 using 3-(4,5-dimethyl2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The methanolic crude extract was subjected to a bioassay guided solvent partitioning and fractionation by vacuum liquid chromatography (VLC) and gravity column chromatography (GCC). The apoptotic effect of the most active fraction was investigated using JC-1 assay to determine mitochondrial membrane alteration and TUNEL assay to detect DNA fragmentation. A. loheri crude extract demonstrated very high cytotoxicity against HCT116 with IC50 value of 0.49±0.07µg/mL. The hexane (ALBH) and ethyl acetate (ALBEA) partitions and most of the VLC and GCC fractions showed high to moderate cytotoxicity. The GCC fraction ALBEA9.2 demonstrated very low IC50 value of 0.04±0.01µg/mL and showed high selectivity index (SI) of 8.72. Morphological examination of HCT116 cells treated with ALBEA9.2 showed loss of membrane integrity and loss of contact with neighboring cells, condensed cytoplasm and detachment from the substratum suggestive of apoptosis. Reduced mitochondrial membrane potential and the presence of genome fragmentation in treated cells confirmed the apoptosis-inducing effect of ALBEA9.2. The study indicates that bark extracts of A. loheri shows cytotoxic activity that is highly selective against HCT116 cell line. The findings suggest the potential of ALBEA9.2 as an anticancer agent by inducing apoptosis.
Asare GA, Bugyei K, Sittie A, Yahaya ES, Gyan B, Adjei S, Addo P, Wiredu EK, Adjei DN, Nyarko AK. 2012. Genotoxicity, cytotoxicity and toxicological evaluation of whole plant extracts of the medicinal plant Phyllanthus niruri (Phyllanthaceae). Genetics and Molecular Research 11, 100-111. DOI: 10.4238/2012.January.13.3
Bézivin C, Tomasi F, Lohézie-Le D, Boustie J. 2003. Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. Phytomedicine 10, 499–503. DOI: 10.1078/094471103322331458
Bohnenstengel FI, Steube KG, Meyer C, Nugroho BW, Hung PD, Kiet LC, Proksch P. 1999. Structure activity relationships of antiproliferative rocaglamide derivatives from Aglaia species (Meliaceae). Zeitschrift für Naturforschung C-A Journal of Biosciences 54, 55-60.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 68, 394-424.
Canoy RJC, Lomanta JMJC, Ballesteros PM, Chun EAC, Dator RP, Jacinto SD. 2011. Cancer chemotherapeutic potential of endemic and indigenous plants of Kanawan, Morong, Bataan Province, Philippines. Asia Life Sciences 20, 331-9.
Cragg GM, Newman DJ. 2005. Plants as a source of anti-cancer agents. Journal of Ethnopharmacology 100, 72-9. DOI: 10.1016/j.jep.2005.05.011
Dapat E, Jacinto S, Efferth T. 2013. A phenolic ester from Aglaia loheri leaves reveals cytotoxicity towards sensitive and multidrug-resistant cancer cells. BMC Complementary and Alternative Medicine 13, 286. DOI: 10.1186/1472-6882-13-286
De Oliveira PF, Alves JM, Damasceno JL, Oliveira RAM, Dias HJ, Crotti AEM, Tavares DC. 2015. Cytotoxicity screening of essential oils in cancer cell lines. Revista Brasileirade Farmacognosia 25, 183-88.
Delie F, Rubas W. 1997. A human colonic cell line sharing similarities with enterocytes as a model to examine oral absorption: advantages and limitations of the Caco-2 model. Critical Reviews in Therapeutic Drug Carrier Systems 14, 221–286. DOI: 10.1615/CritRevTherDrugCarrierSyst.v14.i3.20
Dreyer M, Nugroho BW, Bohnenstengel FI, Ebel R, Wray V, Witte L, Bringmann G, Mühlbacher J, Herold M, Hung D, Kiet C, Proksch P. 2001. New Insecticidal Rocaglamide Derivatives and Related Compounds from Aglaia oligophylla. Journal of Natural Products 64, 415-420. DOI: 10.1021/np000123x
Feitelson MA, Arzumanyan A, Kulathinal RJ, Blain SW, Holcombe RF, Mahajna J, Marino M, Martinez-Chantar ML, Nawroth R, Sanchez-Garcia I, Sharma D, Saxena NK, Singh N, Vlachostergios PJ, Guo S, Honoki K, Fujii H, Georgakilas AG, Bilsland A, Amedei A, Niccolai E, Amin A, Ashraf SS, Boosani CS, Guha G, Ciriolo MR, Aquilano K, Chen S, Mohammed SI, Azmi AS, Bhakta D, Halicka D, Keith WN, Nowsheen S. 2015. Sustained proliferation in cancer: mechanisms and novel therapeutic targets. Seminars in Cancer Biology 35, S25-54.DOI: 10.1016/j.semcancer.2015.02.006.
García-Varela R, Ramírez ORF, Serna-Saldivar SO, Altamirano J, Cardineau GA. 2016. Cancer cell specific cytotoxic effect of Rhoeo discolor extracts and solvent fractions. Journal of Ethnopharmacology 190, 46-58. DOI: 10.1016/j.jep.
Greger H, Zechner G, Hofer O, Vajrodaya SJ. 1996. Infraspecific variation of sulfur-containing bisamides from Aglaia leptantha. Journal of Natural Products 59, 1163-1168. DOI: 10.1021/np990542y
Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell. 144, 646-674. DOI: 10.1016/j.cell.2011.02.013
Herrera A, King RE, Ipulan LA. 2011. Effects of oral administration of crude leaf extracts of Aglaia loheri Blanco and Ardisia pyramidalis (Cav.) Pers on mouse embryo morphology and maternal reproductive performance. Journal of Medicinal Plants Research 5, 3904-3916.
Lopez J, Tait SWG. 2015. Mitochondrial apoptosis: Killing cancer using the enemy within. British Journal of Cancer 112, 957-962. DOI: 10.1038/bjc.2015.85
Manson MM, Farmer PB, Gescher A, Steward WP. 2005. Innovative agents in cancer prevention. Recent Results in Cancer Research 166, 257-275.
Mohamad K, Martin MT, Najdar H, Gaspard C, Sevenet T, Awang K, Hadi H, Païs M. 1999. Cytotoxic 3,4-Secoapotirucallanes from Aglaia argentea bark. Journal of Natural Products 62, 868-872. DOI: 10.1021/np990013u
Mosmann T. 1983. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxic Assays. Journal of Immunological Methods 65, 55-63.
Pan L, Kardono LBS, Riswan S, Chai H, de Blanco EJC, Pannell CM, Soejarto DD, McCloud TG, Newman DJ, Kinghorn AD. 2010. Isolation and Characterization of Minor Analogues of Silvestrol and Other Constituents from a Large-Scale Re-collection of Aglaia foveolata. Journal of Natural Products 7, 1873–1878. DOI: 10.1021/np100503q
Pannell CM. 1998. Aglaia rimosa. The IUCN Red List of Threatened Species 1998:e.T34917A9897290. http://dx.doi.org/10.2305/IUCN.UK.1998.RLTS.T34917A9897290.en. Downloaded on December 2017
Park SU. 2012. Anticancer compounds from plants. EXCLI Journal 11, 386-389.
Pavarini DP, Pavarini SP, Niehues M, Lopes NP. 2012. Exogenous influences on plant secondary metabolite levels. Animal Feed Science and Technology 176, 5-16. https://doi.org/10.1016/j.a
Pfeffer CM, Singh ATK. 2018. Apoptosis: A target for anticancer therapy. International Journal of Molecular Sciences 19, 448. DOI: 10.3390/ijms1902
Prayong P, Barusrux S, Weerapreeyakul N. 2008. Cytotoxic activity screening of some indigenous Thai plants. Fitoterapia 79, 598-601. DOI: 10.1016/j.fitote.2008.06.007
Ragasa CY, Torres OB, Shen C, Mejia MGR, Ferrer RJ and Jacinto SD. 2012. Chemical constituents of Aglaia loheri. Pharmacognosy Journal 4, 29-31. https://doi.org/10.5530/pj.2012.32.6
Rivero-Cruz JF, Chai HB, Kardono LBS, Setyowati FM, Afriatini JJ, Riswan S, Farnsworth NR, Cordell GA, Pezzuto JM, Swanson SM, Kinghorn AD. 2004. Cytotoxic Constituents of the Twigs and Leaves of Aglaia rubiginosa. Journal of Natural Products 67, 343-347. DOI: 10.1021/NP0304417
Sharma PR, Mondhe DM, Muthiah S, Pal HC. 2009. Anticancer activity of an essential oil from Cymbopogon flexuosus. Chemico-Biological Interactions 179, 160-168. DOI: 10.1016/j.cbi.2008.
Suffness M, Pezzuto JM. 1990. Assays related to cancer drug discovery. In: Hostettmann, K. (Ed.), Methods in Plant Biochemistry: Assays for Bioactivity. Academic Press, London pp. 71-133.
Wang TH, Wang HS, Soong YK. 2000. Paclitaxel-induced cell death: where the cell cycle and apoptosis come together. Cancer. 88, 2619-28. https://doi.org/10.1002/1097-0142(20000601)88:11
Wu TS, Liou MJ, Kuoh CS, Teng CM, Nagao T, Lee KH. 1997. Cytotoxic and antiplatelet aggregation principles from Aglaia elliptifolia. Journal of Natural Products 60, 606-608. https://doi.org/10.1021/ 3+
Yuet-Ping K, Darah I, Yusuf UK, Yeng C, Sasidharan S. 2012. Genotoxicity of Euphorbia hirta: an Allium cepa assay. Molecules 17, 7782-7791 DOI: 10.3390/molecules17077782
Norielyn N. Abalos, Sonia D. Jacinto, 2019. Cytotoxicity of bark extracts from Aglaia loheri (Blanco) Merr. (Meliaceae) against human colorectal carcinoma cells (HCT116). Int. J. Biosci., 14(4), 418-427.
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