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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Anticancer Effect and Phytochemical Profile of the Extract from Achillea ketenoglui against Human Colorectal Cancer Cell Lines

Author(s): İlknur Ç. Ayan*, Sümeyra Çetinkaya, Hatice G. Dursun, Canan E. Güneş and Seda Şirin

Volume 22, Issue 9, 2022

Published on: 04 January, 2022

Page: [1769 - 1779] Pages: 11

DOI: 10.2174/1871520621666210908110422

Price: $65

Abstract

Background: In the treatment of Colorectal Cancer (CRC), the search for new antineoplastic drugs with fewer side effects and more effectiveness continues. A significant part of these pursuits and efforts focus on medicinal herbs and plant components derived from these plants. A. ketenoglui is one of these medicinal plants, and its anticancer potential has never been studied before.

Methods: The phenolic and flavonoid content, and antioxidant activity of A. ketenoglui extracts were determined. The phytochemical profiling and quantification analysis of major components were performed by HPLC-ESI-Q-TOF-MS. Cytotoxicity, proliferation, apoptosis and cell cycle were evaluated to reveal the anticancer activity of the extract on CRC cells (HCT 116 and HT-29). The determined anticancer activity was confirmed by mRNA (RT-qPCR) and protein (Western blotting) analyzes.

Results: A. ketenoglui methanol extract was found to have high phenolic (281.89±0.23) and flavonoid (33.80±0.15) content and antioxidant activity (IC50 40.03±0.38). According to the XTT assay, the extract has strong cytotoxic activity (IC50 350 μM in HCT 116 and IC50 263 μM in HT-29 cell line). The compounds most commonly found in the plant are, in descending order, chlorogenic acid, apigenin, genistin, baicalin, eupatorin, casticin, and luteolin. In flowcytometric analysis, the extract was found to induce greater apoptosis and cell cycle arrest in both cell lines than in both control and positive control (casticin). According to the results of the mRNA expression analysis, the extract treatment upregulated the expression of the critical genes of the cell cycle and apoptosis, such as p53, p21, caspase-3, and caspase-9. In protein expression analysis, an increase in caspase-3 and p53 expression was observed in both cell lines treated with the extract. In addition, caspase-9 expression was increased in HT-29 cells.

Conclusion: The findings show that A. ketenoglui has an anticancer potential by inducing apoptosis and arresting the cancer cell cycle and may be promising for CRC therapy. This potential of the plant is realized through the synergistic effects of its newly identified components.

Keywords: Apoptosis, cell cycle, casticin, colorectal cancer, medicinal plants, cytotoxicity, Achilla ketenoglui.

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[1]
Fitzmaurice, C.; Allen, C.; Barber, R.M. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study. JAMA Oncol., 2017, 3(4), 524-548.
[http://dx.doi.org/10.1001/jamaoncol.2016.5688] [PMID: 27918777]
[2]
van der Geest, L.G.; Lam-Boer, J.; Koopman, M.; Verhoef, C.; Elferink, M.A.; de Wilt, J.H. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin. Exp. Metastasis, 2015, 32(5), 457-465.
[http://dx.doi.org/10.1007/s10585-015-9719-0] [PMID: 25899064]
[3]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin., 2019, 69(1), 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[4]
Sisodiya, P.S. Plant derived anticancer agents: A review. Int J Res Dev Pharm L Sci., 2013, 2(2), 293-308.
[5]
Aravindaram, K.; Yang, N-S. Anti-inflammatory plant natural products for cancer therapy. Planta Med., 2010, 76(11), 1103-1117.
[http://dx.doi.org/10.1055/s-0030-1249859] [PMID: 20432202]
[6]
Asensi, M.; Ortega, A.; Mena, S.; Feddi, F.; Estrela, J.M. Natural polyphenols in cancer therapy. Crit. Rev. Clin. Lab. Sci., 2011, 48(5-6), 197-216.
[http://dx.doi.org/10.3109/10408363.2011.631268] [PMID: 22141580]
[7]
Bali, E.B.; Açık, L.; Elçi, P.; Sarper, M.; Avcu, F.; Vural, M. In vitro anti-oxidant, cytotoxic and pro-apoptotic effects of Achillea teretifolia Willd extracts on human prostate cancer cell lines. Pharmacogn. Mag., 2015, 11(Suppl. 2), S308-S315.
[http://dx.doi.org/10.4103/0973-1296.166060] [PMID: 26664020]
[8]
Başer, K.H.C. Essential oils of achillea species of Turkey. Nat Volatiles &Essent Oils., 2016, 3(1), 1-14.
[9]
Honda, G.; Yeşilada, E.; Tabata, M.; Sezik, E.; Fujita, T.; Takeda, Y.; Takaishi, Y.; Tanaka, T. Traditional medicine in Turkey. VI. Folk medicine in west Anatolia: Afyon, Kütahya, Denizli, Muğla, Aydin provinces. J. Ethnopharmacol., 1996, 53(2), 75-87.
[PMID: 8844462]
[10]
Sezik, E.; Yeşilada, E.; Honda, G.; Takaishi, Y.; Takeda, Y.; Tanaka, T. Traditional medicine in Turkey X. Folk medicine in Central Anatolia. J. Ethnopharmacol., 2001, 75(2-3), 95-115.
[http://dx.doi.org/10.1016/S0378-8741(00)00399-8] [PMID: 11297840]
[11]
Kupeli, E.; Orhan, I.; Kusmenoglu, S. Evaluation of anti-inflammatory and antinociceptive activity of five Anatolian Achillea species. Turk J Pharm Sci., 2007, 4(2), 89-99.
[12]
Karabay-Yavasoglu, N.U.; Karamenderes, C.; Baykan, S. Antinociceptive and anti-inflammatory activities and acute toxicity of Achillea nobilis subsp neilreichii extract in mice and rats. Pharm. Biol., 2007, 45(2), 162-168.
[http://dx.doi.org/10.1080/13880200601113149]
[13]
Kordalis, S.; Aslan, I.; Çalmaşur, O. Toxicity of essential oils isolated from three Artemisia species and some of their major components to granary weevil, Sitophilus granarius (L.) (Coleopt.: Curculionidae). Ind. Crops Prod., 2006, 23(2), 162-170.
[http://dx.doi.org/10.1016/j.indcrop.2005.05.005]
[14]
Alfatemi, S.M.H.; Rad, J.S.; Rad, M.S.; Mohsenzadeh, S.; da Silva, J.A. Chemical composition, antioxidant activity and in vitro antibacterial activity of Achillea wilhelmsii C. Koch essential oil on methicillin-susceptible and methicillin-resistant Staphylococcus aureus spp. Biotech., 2015, 5(1), 39-44.
[http://dx.doi.org/10.1007/s13205-014-0197-x] [PMID: 28324358]
[15]
Demirci, F.; Demirci, B.; Gurbuz, I. Characterization and biological activity of Achillea teretifolia Willd. and A. nobilis L. subsp neilreichii (Kerner) Formanek essential oils. Turk. J. Biol., 2009, 33(2), 129-136.
[16]
Jianu, C.; Misca, C.; Muntean, S.G. Composition, antioxidant and antimicrobial activity of the essential oil of Achillea collina Becker growing wild in western Romania. Hem. Ind., 2015, 69(4), 381-386.
[http://dx.doi.org/10.2298/HEMIND140329052J]
[17]
Chávez-Silva, F.; Cerón-Romero, L.; Arias-Durán, L.; Navarrete-Vázquez, G.; Almanza-Pérez, J.; Román-Ramos, R.; Ramírez-Ávila, G.; Perea-Arango, I.; Villalobos-Molina, R.; Estrada-Soto, S. Antidiabetic effect of Achillea millefollium through multitarget interactions: α-glucosidases inhibition, insulin sensitization and insulin secretagogue activities. J. Ethnopharmacol., 2018, 212, 1-7.
[http://dx.doi.org/10.1016/j.jep.2017.10.005] [PMID: 29031783]
[18]
Hormozi, M.; Baharvand, P. Achillea biebersteinni Afan may inhibit scar formation: In vitro study. Mol. Genet. Genomic Med., 2019, 7(5), e640.
[http://dx.doi.org/10.1002/mgg3.640] [PMID: 30968605]
[19]
Ashtiani, M.; Nabatchian, F.; Galavi, H.R.; Saravani, R.; Farajian-Mashhadi, F.; Salimi, S. Effect of Achillea wilhelmsii extract on expression of the human telomerase reverse transcriptase mRNA in the PC3 prostate cancer cell line. Biomed. Rep., 2017, 7(3), 251-256.
[http://dx.doi.org/10.3892/br.2017.956] [PMID: 28811896]
[20]
Papakosta, K.; Grafakou, M.E.; Barda, C.; Kostopoulos, I.V.; Tsitsilonis, O.; Skaltsa, H. Cytotoxicity and anti-cancer activity of the genus Achillea L. Curr. Med. Chem., 2020, 27(41), 6910-6925.
[http://dx.doi.org/10.2174/0929867327666200505092514] [PMID: 32368970]
[21]
Xiao, Z.; Liu, W.; Zhu, G.; Zhou, R.; Niu, Y. A review of the preparation and application of flavour and essential oils microcapsules based on complex coacervation technology. J. Sci. Food Agric., 2014, 94(8), 1482-1494.
[http://dx.doi.org/10.1002/jsfa.6491] [PMID: 24282124]
[22]
Aminkhani, A.; Sharifi, R.; Dorosti, R. Chemical Composition and Antimicrobial Activity of Achillea tenuifolia Lam. Essential Oil at Different Phenological Stages from Khoy. Chem. Biodivers., 2019, 16(12), e1900289.
[http://dx.doi.org/10.1002/cbdv.201900289] [PMID: 31552700]
[23]
Si, X.T.; Zhang, M.L.; Shi, Q.W.; Kiyota, H. Chemical constituents of the plants in the genus Achillea. Chem. Biodivers., 2006, 3(11), 1163-1180.
[http://dx.doi.org/10.1002/cbdv.200690119] [PMID: 17193231]
[24]
Benetis, R.; Radusiene, J.; Janulis, V. Variability of phenolic compounds in flowers of Achillea millefolium wild populations in Lithuania. Medicina (Kaunas), 2008, 44(10), 775-781.
[http://dx.doi.org/10.3390/medicina44100097] [PMID: 19001835]
[25]
Nemeth, E.; Bernath, J. Biological activities of yarrow species (Achillea spp.). Curr. Pharm. Des., 2008, 14(29), 3151-3167.
[http://dx.doi.org/10.2174/138161208786404281] [PMID: 19075697]
[26]
Başer, K.H.C.; Demirci, B.; Duman, H. Composition of the essential oils of two endemic species from turkey: Achillea lycaonica and A. ketenoglui. Chem. Nat. Compd., 2001, 37(3), 245-252.
[http://dx.doi.org/10.1023/A:1012518023780]
[27]
Blois, M.S. Antioxidant determinations by the use of a stable free radical. Nature, 1958, 181, 1199-1200.
[http://dx.doi.org/10.1038/1811199a0]
[28]
Singleton, V.L.; Orthofer, R.; Lamuela-Raventos, R.M. Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent. Methods Enzymol., 1999, 299, 152-178.
[http://dx.doi.org/10.1016/S0076-6879(99)99017-1]
[29]
Moreno, M.I.; Isla, M.I.; Sampietro, A.R.; Vattuone, M.A. Comparison of the free radical-scavenging activity of propolis from several regions of Argentina. J. Ethnopharmacol., 2000, 71(1-2), 109-114.
[http://dx.doi.org/10.1016/S0378-8741(99)00189-0] [PMID: 10904153]
[30]
Eghdami, A.; Sadeghi, F. Determination of total phenolic and flavonoids contents in methanolic and aqueous extract of Achillea millefolium. Org Chem J., 2010, 2, 81-84.
[31]
Benedec, D.; Hanganu, D.; Oniga, I.; Filip, L.; Bischin, C.; Silaghi-Dumitrescu, R.; Tiperciuc, B.; Vlase, L. Achillea schurii flowers: chemical, antioxidant, and antimicrobial investigations. Molecules, 2016, 21(8), 1050.
[http://dx.doi.org/10.3390/molecules21081050] [PMID: 27529204]
[32]
Boutennoun, H.; Boussouf, L.; Rawashdeh, A. In vitro cytotoxic and antioxidant activities of phenolic components of Algerian Achillea odorata leaves. Arab. J. Chem., 2017, 10, 403-409.
[http://dx.doi.org/10.1016/j.arabjc.2014.05.013]
[33]
Stankovic, M.; Petrovic, M.; Godjevac, D. Screening inland halophytes from the central Balkan for their antioxidant activity in relation to total phenolic compounds and flavonoids: Are there any prospective medicinal plants? J. Arid Environ., 2015, 120, 26-32.
[http://dx.doi.org/10.1016/j.jaridenv.2015.04.008]
[34]
Albayrak, S.; Silahtaroğlu, N. Determination of biological activities of essential oil and extract obtained from Achillea coarctata Pour. Advances in Traditional Medicine, 2020, 20, 77-88.
[http://dx.doi.org/10.1007/s13596-019-00378-w]
[35]
Afshari, M.; Rahimmalek, M.; Miroliaei, M. Variation in polyphenolic profiles, antioxidant and antimicrobial activity of different Achillea species as natural sources of antiglycative compounds. Chem. Biodivers., 2018, 15(8), e1800075.
[http://dx.doi.org/10.1002/cbdv.201800075] [PMID: 29779268]
[36]
Patocka1, J.; Navratilova, Z. Achillea fragrantissima: Pharmacology Review. Clin. Oncol. , 2019, 4, 1-5.
[37]
Estévez, S.; Marrero, M.T.; Quintana, J.; Estévez, F. Eupatorin-induced cell death in human leukemia cells is dependent on caspases and activates the mitogen-activated protein kinase pathway. PLoS One, 2014, 9(11), e112536.
[http://dx.doi.org/10.1371/journal.pone.0112536] [PMID: 25390937]
[38]
Yan, X.; Qi, M.; Li, P.; Zhan, Y.; Shao, H. Apigenin in cancer therapy: anti-cancer effects and mechanisms of action. Cell Biosci., 2017, 7, 50.
[http://dx.doi.org/10.1186/s13578-017-0179-x] [PMID: 29034071]
[39]
Wang, Q.; Wang, H.; Jia, Y.; Pan, H.; Ding, H. Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma. Cancer Chemother. Pharmacol., 2017, 79(5), 1031-1041.
[http://dx.doi.org/10.1007/s00280-017-3299-4] [PMID: 28393257]
[40]
Wan, D.; Ouyang, H. Baicalin induces apoptosis in human osteosarcoma cell through ROS-mediated mitochondrial pathway. Nat. Prod. Res., 2018, 32(16), 1996-2000.
[http://dx.doi.org/10.1080/14786419.2017.1359173] [PMID: 28871826]
[41]
Yamagata, K.; Izawa, Y.; Onodera, D.; Tagami, M. Chlorogenic acid regulates apoptosis and stem cell marker-related gene expression in A549 human lung cancer cells. Mol. Cell. Biochem., 2018, 441(1-2), 9-19.
[http://dx.doi.org/10.1007/s11010-017-3171-1] [PMID: 28875417]
[42]
Islam, A.; Islam, M.S.; Uddin, M.N.; Hasan, M.M.I.; Akanda, M.R. The potential health benefits of the isoflavone glycoside genistin. Arch. Pharm. Res., 2020, 43(4), 395-408.
[http://dx.doi.org/10.1007/s12272-020-01233-2] [PMID: 32253713]
[43]
Ramchandani, S.; Naz, I.; Lee, J.H.; Khan, M.R.; Ahn, K.S. An overview of the potential antineoplastic effects of casticin. Molecules, 2020, 25(6), 1287.
[http://dx.doi.org/10.3390/molecules25061287] [PMID: 32178324]
[44]
Haïdara, K.; Zamir, L.; Shi, Q.W.; Batist, G. The flavonoid Casticin has multiple mechanisms of tumor cytotoxicity action. Cancer Lett., 2006, 242(2), 180-190.
[http://dx.doi.org/10.1016/j.canlet.2005.11.017] [PMID: 16387422]
[45]
Kundaković, T.; Stanojković, T.; Juranić, Z.; Kovacević, N. Cytotoxic and antioxidant activity of Achillea alexandri-regis. Pharmazie, 2005, 60(4), 319-320.
[PMID: 15881617]
[46]
Agar, O.T.; Dikmen, M.; Ozturk, N.; Yilmaz, M.A.; Temel, H.; Turkmenoglu, F.P. Comparative studies on phenolic composition, antioxidant, wound healing and cytotoxic activities of selected Achillea L. species growing in Turkey. Molecules, 2015, 20(10), 17976-18000.
[http://dx.doi.org/10.3390/molecules201017976] [PMID: 26437391]
[47]
Navaie, B.A.; Kavoosian, S.; Fattahi, S. Antioxidant and cytotoxic effect of aqueous and hydroalcoholic extracts of the Achillea millefolium L. on MCF-7 breast cancer cell line. Int. Biol. Biomed. J., 2015, 1(3), 119-125.
[48]
Tian, Q.; Zang, Y.H. Antiproliferative and apoptotic effects of the ethanolic herbal extract of Achillea falcata in human cervical cancer cells are mediated via cell cycle arrest and mitochondrial membrane potential loss. J. BUON, 2015, 20(6), 1487-1496.
[PMID: 26854445]
[49]
Galavi, H.R.; Saravani, R.; Shahraki, A.; Ashtiani, M. Anti-proliferative and apoptosis inducing potential of hydroalcoholic Achillea wilhelmsii C. Koch extract on human breast adenocarcinoma cell lines MCF-7 and MDA-Mb-468. Pak. J. Pharm. Sci., 2016, 29(6)(Suppl.), 2397-2403.
[PMID: 28167484]
[50]
García-Risco, M.R.; Mouhid, L.; Salas-Pérez, L.; López-Padilla, A.; Santoyo, S.; Jaime, L.; Ramírez de Molina, A.; Reglero, G.; Fornari, T. Biological activities of asteraceae (Achillea millefolium and Calendula officinalis) and lamiaceae (Melissa officinalis and Origanum majorana) plant extracts. Plant Foods Hum. Nutr., 2017, 72(1), 96-102.
[http://dx.doi.org/10.1007/s11130-016-0596-8] [PMID: 28101823]
[51]
Rezai, M.; Saravani, R.; Sargazi, S.; Moudi, M.; Jafari Shahroudi, M.; Saravani, R. Achillea Wilhelmsii C. KochHydroalcoholic extract induces apoptosis and alters LIN28B and p53 gene expression in hela cervical cancer cells. Rep. Biochem. Mol. Biol., 2019, 8(3), 318-325.
[PMID: 32274404]
[52]
Uzun, K.; Arslan, A.K.K. Turkish endemic Achillea species protect human neuroblastoma SH-SY5Y cells against hydrogen peroxide-induced cytotoxicity. Proceedings, 2019, 40, 43.
[http://dx.doi.org/10.3390/proceedings2019040043]
[53]
Abdalla, A.N.; Shaheen, U.; Abdallah, Q.M.A.; Flamini, G.; Bkhaitan, M.M.; Abdelhady, M.I.S.; Ascrizzi, R.; Bader, A. Proapoptotic activity of Achillea membranacea essential oil and its major constituent 1,8-cineole against A2780 ovarian cancer cells. Molecules, 2020, 25(7), 1582.
[http://dx.doi.org/10.3390/molecules25071582] [PMID: 32235558]
[54]
Pucci, B.; Kasten, M.; Giordano, A. Cell cycle and apoptosis. Neoplasia, 2000, 2(4), 291-299.
[http://dx.doi.org/10.1038/sj.neo.7900101] [PMID: 11005563]
[55]
Igney, F.H.; Krammer, P.H. Death and anti-death: tumour resistance to apoptosis. Nat. Rev. Cancer, 2002, 2(4), 277-288.
[http://dx.doi.org/10.1038/nrc776] [PMID: 12001989]
[56]
Rai, N.K.; Tripathi, K.; Sharma, D.; Shukla, V.K. Apoptosis: a basic physiologic process in wound healing. Int. J. Low. Extrem. Wounds, 2005, 4(3), 138-144.
[http://dx.doi.org/10.1177/1534734605280018] [PMID: 16100094]
[57]
Elmore, S. Apoptosis: a review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[58]
Zhu, L.; Lu, Z.; Zhao, H. Antitumor mechanisms when pRb and p53 are genetically inactivated. Oncogene, 2015, 34(35), 4547-4557.
[http://dx.doi.org/10.1038/onc.2014.399] [PMID: 25486431]
[59]
Tokino, T.; Nakamura, Y. The role of p53-target genes in human cancer. Crit. Rev. Oncol. Hematol. 2000, 33(1), 1-6.
[http://dx.doi.org/10.1016/S1040-8428(99)00051-7] [PMID: 10714958]

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