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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

A Study of Ungernia trisphaera Bunge and Thymus transcaspicus Cytotoxicity in Cancer Cell Lines

Author(s): Roghayeh Rashidi, Amir R. Afshari, Shirin Ghasemian, Mohammad Soukhtanloo, Mohammad Sadegh Amiri and Seyed Hadi Mousavi*

Volume 20, Issue 3, 2023

Published on: 15 July, 2022

Page: [279 - 290] Pages: 12

DOI: 10.2174/1570180819666220513144047

Price: $65

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Abstract

Objective: Thymus transcaspicus (Lamiaceae) is an Iranian species of Thymus, and Ungernia trisphaera Bunge belongs to the family Amaryllidaceae. Cytotoxic properties of total ethanolic extract of T. transcaspicus and U. trisphaera were investigated against different cell lines including B16F10, PC3, U87, and MCF-7.

Methods: The proliferation, cell cycle, and migration of the cells were determined by thiazolyl blue tetrazolium bromide (MTT) test, propidium iodide (PI) staining, and scratch assay respectively. The effects of U. trisphaera extract (UTE) on the activity of matrix metalloproteinases (MMPs) and angiogenesis were evaluated by the gelatin zymography method and chicken chorioallantoic membrane model, respectively. The GSH, SOD, and MDA were evaluated by colorimetric method.

Results: The results showed that UTE could inhibit the development of malignant cells in a concentration- dependent manner, while the inhibitory effect of T. transcaspicus extract (TTE) was not significant compared to the control group. The UTE-induced sub-G1 peak apoptosis compared to the control group indicated that apoptotic cell death is involved in UTE-induced cytotoxicity. MMPs activity was significantly decreased 48 hours after treatment. Moreover, GSH level and SOD activity were significantly decreased while MDA and ROS levels were significantly increased after 24 hours treatment. In addition, combination of UTE (1.5-25 μg/mL) with doxorubicin (6 μg/mL) showed an additive cell growth inhibitory effect.

Conclusion: UTE demonstrated cytotoxic and apoptogenic effects in different cancer cell lines, and it was found that apoptosis plays a crucial role in the cytotoxicity of UTE. Thus, U. trisphaera can be considered a potential medicinal herb in cancer treatment after comprehensive pharmacological and toxicological studies.

Keywords: Thymus transcaspicus, ungernia trisphaera, cytotoxicity, apoptosis, apoptogenic, cancer cell lines.

« Previous Next »
[1]
Huang, M.; Lu, J.J.; Ding, J. Natural products in cancer therapy: Past, present and future. Nat. Prod. Bioprospect., 2021, 11(1), 5-13.
[http://dx.doi.org/10.1007/s13659-020-00293-7] [PMID: 33389713]
[2]
Sadeghnia, H.R.; Jamshidi, R.; Afshari, A.R.; Mollazadeh, H.; Forouzanfar, F.; Rakhshandeh, H. Terminalia chebula attenuates quinolinate-induced oxidative PC12 and OLN-93 cell death. Mult. Scler. Relat. Disord., 2017, 14, 60-67.
[http://dx.doi.org/10.1016/j.msard.2017.03.012] [PMID: 28619434]
[3]
Zhu, S.; Yu, Q.; Huo, C.; Li, Y.; He, L.; Ran, B.; Chen, J.; Li, Y.; Liu, W. Ferroptosis: a novel mechanism of artemisinin and its derivatives in cancer therapy. Curr. Med. Chem., 2021, 28(2), 329-345.
[http://dx.doi.org/10.2174/0929867327666200121124404] [PMID: 31965935]
[4]
Mollazadeh, H.; Afshari, A.R.; Hosseinzadeh, H. Review on the potential therapeutic roles of nigella sativa in the treatment of patients with cancer: Involvement of apoptosis:-black cumin and cancer. J. Pharmacopuncture, 2017, 20(3), 158-172.
[http://dx.doi.org/10.3831/KPI.2017.20.019] [PMID: 30087792]
[5]
Afshari, A.R.; Roshan, M.K.; Soukhtanloo, M.; Askari, V.R.; Mollazadeh, H.; Nik, M.J.; Yazdi, A.A.; Kia, F.A.; Mousavi, S.H. Investigation of cytotoxic and apoptogenic effects of terminalia chebula hydro-alcoholic extract on glioblastoma cell line. Shefaye Khatam, 2018, 5(4), 14-23.
[http://dx.doi.org/10.29252/shefa.6.4.14]
[6]
Afshari, A.R.; Karimi Roshan, M.; Soukhtanloo, M.; Ghorbani, A.; Rahmani, F.; Jalili-Nik, M.; Vahedi, M.M.; Hoseini, A.; Sadeghnia, H.R.; Mollazadeh, H.; Mousavi, S.H. Cytotoxic effects of auraptene against a human malignant glioblastoma cell line. Avicenna J. Phytomed., 2019, 9(4), 334-346.
[PMID: 31309072]
[7]
Taraphdar, A.K.; Roy, M.; Bhattacharya, R. Natural products as inducers of apoptosis: Implication for cancer therapy and prevention. Curr. Sci., 2001, 11(10), 1387-1396.
[8]
Mousavi, S.H.; Tavakkol-Afshari, J.; Brook, A.; Jafari-Anarkooli, I. Role of caspases and Bax protein in saffron-induced apoptosis in MCF-7 cells. Food Chem. Toxicol., 2009, 47(8), 1909-1913.
[http://dx.doi.org/10.1016/j.fct.2009.05.017] [PMID: 19457443]
[9]
Morales, R. The history, botany and taxonomy of the genus Thymus. Thyme: the genus. Thymus, 2002, CRC Press, 1-43.
[10]
Sefidkon, F.; Dabiri, M. Rahimi-Bidgoly, A. The effect of distillation methods and stage of plant growth on the essential oil content and composition of Thymus kotschyanus Boiss. & Hohen. Flavour Fragrance J., 1999, 14(6), 405-408.
[http://dx.doi.org/10.1002/(SICI)1099-1026(199911/12)14:6<405:AID-FFJ853>3.0.CO;2-M]
[11]
Dargahi, L.; Razavi-Azarkhiavi, K.; Ramezani, M.; Abaee, M.R.; Behravan, J. Insecticidal activity of the essential oil of Thymus transcaspicus against Anopheles stephensi. Asian Pac. J. Trop. Biomed., 2014, 4, 589-591.
[http://dx.doi.org/10.12980/APJTB.4.2014APJTB-2014-0077]
[12]
Miri, R.; Ramezani, M.; Javidnia, K.; Ahmadi, L. Composition of the volatile oil of Thymus transcaspicus Klokov from Iran. Flavour Fragrance J., 2002, 17(4), 245-246.
[http://dx.doi.org/10.1002/ffj.1104]
[13]
Abaza, M.S.I.; Orabi, K.Y.; Al-Quattan, E.; Al-Attiyah, R.J. Growth inhibitory and chemo-sensitization effects of naringenin, a natural flavanone purified from Thymus vulgaris, on human breast and colorectal cancer. Cancer Cell Int., 2015, 15(1), 46.
[http://dx.doi.org/10.1186/s12935-015-0194-0] [PMID: 26074733]
[14]
Esmaeili-Mahani, S.; Falahi, F.; Yaghoobi, M.M. Proapoptotic and antiproliferative effects of Thymus caramanicus on human breast cancer cell line (MCF-7) and its interaction with anticancer drug vincristine. Evid. Based Complement. Alternat. Med., 2014, 2014, 893247.
[http://dx.doi.org/10.1155/2014/893247] [PMID: 24812569]
[15]
Elaissi, A.; Elsharkawy, E.; El Mokni, R.; Debbabi, H.; Brighenti, V.; Nardoni, S.; Pellati, F.; Hammami, S. Chemical composition, antifungal and antiproliferative activities of essential oils from Thymus numidicus L. Nat. Prod. Res., 2021, 35(24), 5888-5893.
[http://dx.doi.org/10.1080/14786419.2020.1800697] [PMID: 32748632]
[16]
Niksic, H.; Becic, F.; Koric, E.; Gusic, I.; Omeragic, E.; Muratovic, S.; Miladinovic, B.; Duric, K. Cytotoxicity screening of Thymus vulgaris L. essential oil in brine shrimp nauplii and cancer cell lines. Sci. Rep., 2021, 11(1), 13178.
[http://dx.doi.org/10.1038/s41598-021-92679-x] [PMID: 34162964]
[17]
Butt, A.S.; Nisar, N.; Ghani, N.; Altaf, I.; Mughal, T.A. Isolation of thymoquinone from Nigella sativa L. and Thymus vulgaris L., and its anti-proliferative effect on HeLa cancer cell lines. Trop. J. Pharm. Res., 2019, 18(1), 37-42.
[http://dx.doi.org/10.4314/tjpr.v18i1.6]
[18]
Bashir, R.; Ahmad Zargar, O.; Hamid Dar, A.; Yedukondalu, N.; Parvaiz, Q.; Hamid, R. The modulation of PI3K/Akt pathway by 3β hydroxylup-12-en-28-oic acid isolated from Thymus linearis induces cell death in HCT-116 cells. Chem. Biol. Drug Des., 2022, 99(1), 162-178.
[http://dx.doi.org/10.1111/cbdd.13957] [PMID: 34558199]
[19]
Bublyk, E.; Adonin, V.; Kunakh, V. Cytogenetic variability of cell lines of Ungernia victoris grown on nutrient media of different compositions. Cytol. Genet., 2008, 42(1), 23-29.
[http://dx.doi.org/10.1007/s11956-008-1004-6]
[20]
Weng, Z.Y.; Wang, Z.Y.; Yan, X.M. A new antitumour agent ungeremine (AT-1840) and its structure-activity relationship. Yao Xue Xue Bao. Acta Pharmaceutica. Sinica., 1982, 17(10), 744-749.
[PMID: 7168322]
[21]
Aranda, A.; Sequedo, L.; Tolosa, L.; Quintas, G.; Burello, E.; Castell, J.V.; Gombau, L. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay: a quantitative method for oxidative stress assessment of nanoparticle-treated cells. Toxicol. In Vitro, 2013, 27(2), 954-963.
[http://dx.doi.org/10.1016/j.tiv.2013.01.016] [PMID: 23357416]
[22]
Zhang, Z.; Lv, Z.; Shao, Y.; Qiu, Q.; Zhang, W.; Duan, X.; Li, Y.; Li, C. Microsomal glutathione transferase 1 attenuated ROS-induced lipid peroxidation in Apostichopus japonicus. Dev. Comp. Immunol., 2017, 73, 79-87.
[http://dx.doi.org/10.1016/j.dci.2017.03.011] [PMID: 28302499]
[23]
Ka, H.; Park, H.J.; Jung, H.J.; Choi, J.W.; Cho, K.S.; Ha, J.; Lee, K.T. Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells. Cancer Lett., 2003, 196(2), 143-152.
[http://dx.doi.org/10.1016/S0304-3835(03)00238-6] [PMID: 12860272]
[24]
Keshavarz, P.; Nobakht, M. Gh, B.F.; Mirhafez, S.R.; Nematy, M.; Azimi-Nezhad, M.; Afin, S.A.; Esmaily, H.; Pourali, L.; Hakak, A.M.; Soukhtanloo, M.; Mirteimouri, M.; Ghomian, N.; Ferns, G.A. Alterations in Lipid Profile, Zinc and Copper Levels and Superoxide Dismutase Activities in Normal Pregnancy and Preeclampsia. Am. J. Med. Sci., 2017, 353(6), 552-558.
[http://dx.doi.org/10.1016/j.amjms.2017.03.022] [PMID: 28641718]
[25]
Gomolin, I.H.; Smith, C.; Jeitner, T.M. Cholinesterase inhibitors: applying pharmacokinetics to clinical decision making. Am. J. Geriatr. Pharmacother., 2011, 9(4), 259-263.
[http://dx.doi.org/10.1016/j.amjopharm.2011.06.001] [PMID: 21763214]
[26]
Martin, S.F. The amaryllidaceae alkaloids. The Alkaloids: Chem Pharmacol. 30; Elsevier, 1987, pp. 251-376.
[27]
Ferdausi, A.; Chang, X.; Hall, A.; Jones, M. Galanthamine production in tissue culture and metabolomic study on Amaryllidaceae alkaloids in Narcissus pseudonarcissus cv. Carlton. Ind. Crops Prod., 2020, 144, 112058.
[http://dx.doi.org/10.1016/j.indcrop.2019.112058]
[28]
Treasure, J. Herbal medicine and cancer: an introductory overview. Seminars in oncology nursing; Elsevier, 2005.
[http://dx.doi.org/10.1016/j.soncn.2005.04.006]
[29]
Cragg, G.M.; Newman, D.J.; Snader, K.M. Natural products in drug discovery and development. J. Nat. Prod., 1997, 60(1), 52-60.
[http://dx.doi.org/10.1021/np9604893] [PMID: 9014353]
[30]
Valeriote, F.; Grieshaber, C.K.; Media, J.; Pietraszkewicz, H.; Hoffmann, J.; Pan, M.; McLaughlin, S. Discovery and development of anticancer agents from plants. J. Exp. Ther. Oncol., 2002, 2(4), 228-236.
[http://dx.doi.org/10.1046/j.1359-4117.2002.01038.x] [PMID: 12416027]
[31]
Sengupta, S.; Toh, S.A.; Sellers, L.A.; Skepper, J.N.; Koolwijk, P.; Leung, H.W.; Yeung, H.W.; Wong, R.N.; Sasisekharan, R.; Fan, T.P. Modulating angiogenesis: the yin and the yang in ginseng. Circulation, 2004, 110(10), 1219-1225.
[http://dx.doi.org/10.1161/01.CIR.0000140676.88412.CF] [PMID: 15337705]
[32]
Mbaveng, A.T.; Chi, G.F.; Bonsou, I.N.; Ombito, J.O.; Yeboah, S.O.; Kuete, V.; Efferth, T. Cytotoxic phytochemicals from the crude extract of Tetrapleura tetraptera fruits towards multi-factorial drug resistant cancer cells. J. Ethnopharmacol., 2021, 267, 113632.
[http://dx.doi.org/10.1016/j.jep.2020.113632] [PMID: 33253828]
[33]
Al-Menhali, A.; Al-Rumaihi, A.; Al-Mohammed, H.; Al-Mazrooey, H.; Al-Shamlan, M.; AlJassim, M.; Al-Korbi, N.; Eid, A.H. Thymus vulgaris (thyme) inhibits proliferation, adhesion, migration, and invasion of human colorectal cancer cells. J. Med. Food, 2015, 18(1), 54-59.
[http://dx.doi.org/10.1089/jmf.2013.3121] [PMID: 25379783]
[34]
Doosti, M-H.; Ahmadi, K.; Fasihi-Ramandi, M. The effect of ethanolic extract of Thymus kotschyanus on cancer cell growth in vitro and depression-like behavior in the mouse. J. Tradit. Complement. Med., 2017, 8(1), 89-94.
[http://dx.doi.org/10.1016/j.jtcme.2017.03.003] [PMID: 29321994]
[35]
Khoschsorur, G.; Winklhofer-Roob, B.; Rabl, H.; Auer, T.; Peng, Z.; Schaur, R. Evaluation of a sensitive HPLC method for the determination of malondialdehyde, and application of the method to different biological materials. Chromatographia, 2000, 52(3-4), 181-184.
[http://dx.doi.org/10.1007/BF02490453]
[36]
Afonso, V.; Champy, R.; Mitrovic, D.; Collin, P.; Lomri, A. Reactive oxygen species and superoxide dismutases: role in joint diseases. Joint Bone Spine, 2007, 74(4), 324-329.
[http://dx.doi.org/10.1016/j.jbspin.2007.02.002] [PMID: 17590367]
[37]
Afshari, A.R.; Jalili-Nik, M.; Soukhtanloo, M.; Ghorbani, A.; Sadeghnia, H.R.; Mollazadeh, H.; Karimi Roshan, M.; Rahmani, F.; Sabri, H.; Vahedi, M.M.; Mousavi, S.H. Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells: role of reactive oxygen species (ROS). EXCLI J., 2019, 18, 576-590.
[PMID: 31611741]
[38]
Bröker, L.E.; Kruyt, F.A.; Giaccone, G. Cell death independent of caspases: a review. Clin. Cancer Res., 2005, 11(9), 3155-3162.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2223] [PMID: 15867207]
[39]
Mousavi, S.H.; Tayarani-Najaran, Z.; Hersey, P. Apoptosis: from signalling pathways to therapeutic tools. Iran. J. Basic Med. Sci., 2008, 11(3), 121-142.
[40]
Brohem, C.A.; Sawada, T.C.; Massaro, R.R.; Almeida, R.L.; Rivelli, D.P.; Ropke, C.D.; da Silva, V.V.; de Lima, T.M.; Curi, R.; Barros, S.B.; Maria-Engler, S.S. Apoptosis induction by 4-nerolidylcatechol in melanoma cell lines. Toxicol. In Vitro, 2009, 23(1), 111-119.
[http://dx.doi.org/10.1016/j.tiv.2008.11.004] [PMID: 19059332]

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