Taraxacum officinale Extracts Exhibit Safe and Selective Anticancer Activity

Article ID: e160921187741 Pages: 9

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Abstract

Background: Medicinal plants have been the primary source of treatment for many diseases. Taraxacum officinale (dandelion), has been used for hundreds of years as a traditional medical remedy for several diseases. However, the anti-cancer potential of this plant has not been fully screened. Genotoxicity screening, which is an integral part of the evaluation of the safety of this plant, is also lacking.

Objective: The aim of this study was to investigate the cytotoxic and genotoxic effects of different extracts of T. officinale.

Methods: The plant sample was extracted in different solvents to prepare ethanol, methanol, chloroform, and water extracts. These extracts were then tested for their ability to inhibit the proliferation of colorectal cancer (Caco-2), chronic myelogenous leukemia (K562), prostate cancer (PC-3), and breast cancer (MCF-7) cells. Cell viability was evaluated using MTT assay, and the selectivity indices were determined with the aid of mortal human fibroblasts. Then the most active extract, chloroform extract, was used to detect the genotoxicity of the constituents on mice bone marrow cells.

Results: The results showed that the T. officinale chloroform extract was found to be most effective against leukemia (K562) and Prostate Cancer (PC-3) cell lines. The extracts showed marked selectivity towards these cancer cells. Genotoxic studies revealed that genotoxic changes occurred after chloroform extract treatment; however, these changes were observed at very high concentrations only.

Conclusion: The results suggest that T. officinale exhibits selective anti-tumor activity, and it is safe for use.

Keywords: Taraxacum officinale, dandelion, cancer, cytotoxicity, genotoxicity, leukemia.

Graphical Abstract

[1]
Sponchiado, G.; Adam, M.L.; Silva, C.D.; Soley, B.S.; de Mello-Sampayo, C.; Cabrini, D.A.; Correr, C.J.; Otuki, M.F. Quantitative genotoxicity assays for analysis of medicinal plants: A systematic review. J. Ethnopharmacol., 2016, 178(1), 289-296.
[http://dx.doi.org/10.1016/j.jep.2015.10.026] [PMID: 26680588]
[2]
Rashid, S.; Ahmad, M.; Zafar, M.; Anwar, A.; Sultana, S.; Tabassum, S.; Ahmed, S.N. Ethnopharmacological evaluation and antioxidant activity of some important herbs used in traditional medicines. J. Tradit. Chin. Med., 2016, 36(5), 689-694.
[http://dx.doi.org/10.1016/S0254-6272(16)30091-7] [PMID: 29949320]
[3]
Msomi, NZ; Simelane, MB Herbal Medicine. Herbal Medicine: Intech Open, London, England, 2019.
[4]
Daniela, A.; Pichichero, E.; Canuti, L.; Cicconi, R.; Karou, D.; D’Arcangelo, G. Identification of phenolic compounds from medicinal and melliferous plants and their cytotoxic activity in cancer cells. Caryologia, 2007, 60(1-2), 90-95.
[http://dx.doi.org/10.1080/00087114.2007.10589552]
[5]
Ahmad, R.; Ahmad, N.; Naqvi, A.A.; Shehzad, A.; Al-Ghamdi, M.S. Role of traditional islamic and arabic plants in cancer therapy. J. Tradit. Complement. Med., 2016, 7(2), 195-204.
[http://dx.doi.org/10.1016/j.jtcme.2016.05.002] [PMID: 28417090]
[6]
Appendino, G.; Minassi, A.; Taglialatela-Scafati, O. Recreational drug discovery: Natural products as lead structures for the synthesis of smart drugs. Nat. Prod. Rep., 2014, 31(7), 880-904.
[http://dx.doi.org/10.1039/c4np00010b] [PMID: 24823967]
[7]
Martinez, M.; Poirrier, P.; Chamy, R.; Prüfer, D.; Schulze- Gronover, C.; Jorquera, L.; Ruiz, G. Taraxacum officinale and related species: An ethnopharmacological review and its potential as a commercial medicinal plant. J. Ethnopharmacol., 2015, 169(1), 244-262.
[http://dx.doi.org/10.1016/j.jep.2015.03.067] [PMID: 25858507]
[8]
Flores-Ocelotl, M.R.; Rosas-Murrieta, N.H.; Moreno, D.A.; Vallejo-Ruiz, V.; Reyes-Leyva, J.; Domínguez, F.; Santos-López, G. Taraxacum officinale and Urtica dioica extracts inhibit dengue virus serotype 2 replication in vitro. BMC Complement. Altern. Med., 2018, 18(1), 95.
[http://dx.doi.org/10.1186/s12906-018-2163-3] [PMID: 29548293]
[9]
Mingarro, D.M.; Plaza, A.; Galán, A.; Vicente, J.A.; Martínez, M.P.; Acero, N. The effect of five Taraxacum species on in vitro and in vivo antioxidant and antiproliferative activity. Food Funct., 2015, 6(8), 2787-2793.
[http://dx.doi.org/10.1039/C5FO00645G] [PMID: 26158347]
[10]
Hfaiedh, M.; Brahmi, D.; Zourgui, L. Hepatoprotective effect of Taraxacum officinale leaf extract on sodium dichromate-induced liver injury in rats. Environ. Toxicol., 2016, 31(3), 339-349.
[http://dx.doi.org/10.1002/tox.22048] [PMID: 25270677]
[11]
Sultana, S.; Asif, H.M.; Nazar, H.M.; Akhtar, N.; Rehman, J.U.; Rehman, R.U. Medicinal plants combating against cancer: A green anticancer approach. Asian Pac. J. Cancer Prev., 2014, 15(11), 4385-4394.
[http://dx.doi.org/10.7314/APJCP.2014.15.11.4385] [PMID: 24969858]
[12]
Greenwell, M.; Rahman, P.K. Medicinal plants: their use in anticancer treatment. Int. J. Pharma Sci., 2015, 6(10), 4103-4112.
[PMID: 26594645]
[13]
Ekor, M. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front. Pharmacol., 2014, 4, 177.
[http://dx.doi.org/10.3389/fphar.2013.00177] [PMID: 24454289]
[14]
Zhou, J.; Ouedraogo, M.; Qu, F.; Duez, P. Potential genotoxicity of traditional chinese medicinal plants and phytochemicals: An overview. Phytother. Res., 2013, 27(12), 1745-1755.
[http://dx.doi.org/10.1002/ptr.4942] [PMID: 23420770]
[15]
Phillips, D.H.; Arlt, V.M. Genotoxicity: Damage to DNA and its consequences. Mol. Clin. Environ. Toxicol., 2009, 2009, 87-110.
[16]
Ovadje, P.; Ammar, S.; Guerrero, J-A.; Arnason, J.T.; Pandey, S. Dandelion root extract affects colorectal cancer proliferation and survival through the activation of multiple death signalling pathways. Oncotarget, 2016, 7(45), 73080-73100.
[http://dx.doi.org/10.18632/oncotarget.11485] [PMID: 27564258]
[17]
Ovadje, P.; Hamm, C.; Pandey, S. Efficient induction of extrinsic cell death by dandelion root extract in human chronic myelomonocytic leukemia (CMML) cells. PLoS One, 2012, 7(2), e30604.
[http://dx.doi.org/10.1371/journal.pone.0030604] [PMID: 22363452]
[18]
Sigstedt, S.C.; Hooten, C.J.; Callewaert, M.C.; Jenkins, A.R.; Romero, A.E.; Pullin, M.J.; Kornienko, A.; Lowrey, T.K.; Slambrouck, S.V.; Steelant, W.F. Evaluation of aqueous extracts of Taraxacum officinale on growth and invasion of breast and prostate cancer cells. Int. J. Oncol., 2008, 32(5), 1085-1090.
[http://dx.doi.org/10.3892/ijo.32.5.1085] [PMID: 18425335]
[19]
Guide for the Care and Use of Laboratory Animals: Eighth editionNational Academies Press: Washington, D.C., 2011.
[20]
Lorke, D. A new approach to practical acute toxicity testing. Arch. Toxicol., 1983, 54(4), 275-287.
[http://dx.doi.org/10.1007/BF01234480] [PMID: 6667118]
[21]
Rossi, A.M.; Romano, M.; Zaccaro, L.; Pulci, R.; Salmona, M. DNA synthesis, mitotic index, drug-metabolising systems and cytogenetic analysis in regenerating rat liver. Comparison with bone marrow test after ‘in vivo’ treatment with cyclophosphamide. Mutat. Res., 1987, 182(2), 75-82.
[http://dx.doi.org/10.1016/0165-1161(87)90056-2] [PMID: 3561429]
[22]
Dobson, K.R.; Reading, L.; Haberey, M.; Marine, X.; Scutt, A. Centrifugal isolation of bone marrow from bone: An improved method for the recovery and quantitation of bone marrow osteoprogenitor cells from rat tibiae and femurae. Calcif. Tissue Int., 1999, 65(5), 411-413.
[http://dx.doi.org/10.1007/s002239900723] [PMID: 10541770]
[23]
Abderrahman, S.M.; Modallal, N. Genotoxic effects of Catha edulis (Khat) extract on mice bone marrow cells. Jordan J. Biol. Sci., 2008, 1(4), 165-172.
[24]
Hart, J.W.; Engberg-Pedersen, H. Statistics of the mouse bone- marrow micronucleus test: Counting, distribution and evaluation of results. Mutat Res-Fund Mol M., 1983, 111(2), 195-207.
[http://dx.doi.org/10.1016/0027-5107(83)90063-5] [PMID: 6633550]
[25]
Allen, J.W.; Shuler, C.F.; Latt, S.A. Bromodeoxyuridine tablet methodology for in vivo studies of DNA synthesis. Somatic Cell Genet., 1978, 4(4), 393-405.
[http://dx.doi.org/10.1007/BF01538862] [PMID: 356290]
[26]
Goto, K.; Maeda, S.; Kano, Y.; Sugiyama, T. Factors involved in differential Giemsa-staining of sister chromatids. Chromosoma, 1978, 66(4), 351-359.
[http://dx.doi.org/10.1007/BF00328535] [PMID: 77756]
[27]
Ackova, D.G.; Kadifkova-Panovska, T.; Andonovska, K.B.; Stafilov, T. Evaluation of genotoxic variations in plant model systems in a case of metal stressors. J. Environ. Sci. Heal., 2016, 51(5), 340-349.
[http://dx.doi.org/10.1080/03601234.2015.1128747] [PMID: 26853058]
[28]
Manosroi, A.; Akazawa, H.; Akihisa, T.; Jantrawut, P.; Kitdamrongtham, W.; Manosroi, W.; Manosroi, J. In vitro anti-proliferative activity on colon cancer cell line (HT-29) of Thai medicinal plants selected from Thai/Lanna medicinal plant recipe database “MANOSROI III”. J. Ethnopharmacol., 2015, 161, 11-17.
[http://dx.doi.org/10.1016/j.jep.2014.11.038] [PMID: 25481081]
[29]
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]
[30]
Colle, D.; Arantes, L.P.; Gubert, P.; da Luz, S.C.A.; Athayde, M.L.; Teixeira Rocha, J.B.; Soares, F.A. Antioxidant properties of Taraxacum officinale leaf extract are involved in the protective effect against hepatoxicity induced by acetaminophen in mice. J. Med. Food, 2012, 15(6), 549-556.
[http://dx.doi.org/10.1089/jmf.2011.0282] [PMID: 22424457]
[31]
Oran, S.; Al-Eisawi, D. Check-list of medicinal plants in Jordan. Dirasat, 1998, 25(2), 84-112.
[32]
Afifi-Yazar, F.U.; Kasabri, V.; Abu-Dahab, R. Medicinal plants from Jordan in the treatment of cancer: traditional uses vs. in vitro and in vivo evaluations-part 1. Planta Med., 2011, 77(11), 1203-1209.
[http://dx.doi.org/10.1055/s-0030-1270832] [PMID: 21347997]
[33]
Choi, E.J.; Kim, G.H. Dandelion (Taraxacum officinale) flower ethanol extract inhibits cell proliferation and induces apoptosis in human ovarian cancer SK-OV-3 cells. Food Sci. Biotechnol., 2009, 18, 552-555.
[34]
Rehman, G.; Hamayun, M.; Iqbal, A.; Khan, S.A.; Khan, H.; Shehzad, A.; Khan, A.L.; Hussain, A.; Kim, H.Y.; Ahmad, J.; Ahmad, A.; Ali, A.; Lee, I.J. Effect of methanolic extract of dandelion roots on cancer cell lines and AMP-activated protein kinase pathway. Front. Pharmacol., 2017, 8, 875.
[http://dx.doi.org/10.3389/fphar.2017.00875] [PMID: 29234282]
[35]
Edori, O; Marcus, A; Maduagu, M. Phytochemical and anti-microbial screening of Phyllantus fratenus and Taraxacuim officinale Leaves. Biochem Anal Biochem., 2019, 8(376), 2161.
[36]
Koh, Y.J.; Cha, D.S.; Ko, J.S.; Park, H.J.; Choi, H.D. Anti-inflammatory effect of Taraxacum officinale leaves on lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells. J. Med. Food, 2010, 13(4), 870-878.
[http://dx.doi.org/10.1089/jmf.2009.1249] [PMID: 20673058]
[37]
da Silva, I.C.V.; Kaluđerović, G.N.; de Oliveira, P.F.; Guimarães, D.O.; Quaresma, C.H.; Porzel, A.; Muzitano, M.F.; Wessjohann, L.A.; Leal, I.C.R. Apoptosis caused by triterpenes and phytosterols and antioxidant activity of an enriched flavonoid extract from Passiflora mucronata. Anticancer. Agents Med. Chem., 2018, 18(10), 1405-1416.
[http://dx.doi.org/10.2174/1871520618666180315090949] [PMID: 29542423]
[38]
Menke, K.; Schwermer, M.; Felenda, J.; Beckmann, C.; Stintzing, F.; Schramm, A.; Zuzak, T.J. Taraxacum officinale extract shows antitumor effects on pediatric cancer cells and enhance mistletoe therapy. Complement. Ther. Med., 2018, 40, 158-164.
[http://dx.doi.org/10.1016/j.ctim.2018.03.005] [PMID: 30219442]
[39]
Wirngo, F.E.; Lambert, M.N.; Jeppesen, P.B. The physiological effects of dandelion (Taraxacum officinale) in type 2 diabetes. Rev. Diabet. Stud., 2016, 13(2-3), 113-131.
[http://dx.doi.org/10.1900/RDS.2016.13.113] [PMID: 28012278]
[40]
Wilson, D.M., III; Thompson, L.H. Molecular mechanisms of sister-chromatid exchange. Mutat. Res-Fund Mol. M., 2007, 616(1-2), 11-23.
[http://dx.doi.org/10.1016/j.mrfmmm.2006.11.017] [PMID: 17157333]
[41]
Abderrahman, S.M.; Shbailat, S.J. Genotoxic and cytotoxic effects of Artemisia herba-alba on mammalian cells. Caryologia, 2014, 67(4), 265-272.
[http://dx.doi.org/10.1080/0144235X.2014.974355]
[42]
Jordan, M.A.; Thrower, D.; Wilson, L. Mechanism of inhibition of cell proliferation by Vinca alkaloids. Cancer Res., 1991, 51(8), 2212-2222.
[PMID: 2009540]