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Current Signal Transduction Therapy

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ISSN (Print): 1574-3624
ISSN (Online): 2212-389X

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Research Article

Wild Thyme Herbal Infusion Consumption Suppresses Tumor Growth in a Murine Model of Breast Cancer

Author(s): Israa A. AL-Ataby and Wamidh H. Talib*

Volume 17, Issue 2, 2022

Published on: 05 July, 2022

Article ID: e290322202771 Pages: 14

DOI: 10.2174/1574362417666220329152528

Price: $65

Abstract

Background: Wild thyme (Thymus serpyllum) belongs to the Lamiaceae family. They were used traditionally to treat different sorts of diseases, including cancer.

Aims: The current study aims to evaluate both anticancer and immunomodulatory activities of wild thyme water extract.

Methods: The antiproliferative activities of the extract were tested against different cancer cell lines using MTT assay, while the degree of apoptosis induction and VEGF expression were detected using ELISA. The lymphocyte proliferation assay was used to evaluate the acquired immunity, whereas both: the nitro blue tetrazolium assay and the neutral red method were used to assess the innate activity; phagocytosis and pinocytosis, respectively. Balb/C mice were inoculated with the EMT6/P breast cancer cells and received the extract orally for 14 days. GC-MS and LC-MS were used to determine the composition of the wild thyme water extract.

Results: Results showed that wild thyme had significant apoptosis induction and angiogenesis suppression effects. The extract stimulated lymphocyte proliferation, phagocytosis and pinocytosis strongly. Seventy percent (70%) of the mice taking this extract did not develop tumors, with a percentage of tumor reduction (49.4%). Rosmarinic acid was the highest in the wild thyme water extract in GC-MS and LCMS.

Conclusion: Wild thyme herbal infusion is rich in phytochemicals that have the potential to activate the immune system and inhibit tumor progression. Further testing is required to understand the exact molecular mechanisms of this extract. Further studies are also needed to test the wild thyme infusion against tumors established in mice.

Keywords: herbal infusions, breast cancer, functional food, mouse model, wild thyme, lamiaceae family.

Graphical Abstract

[1]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 can-cers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Lin SR, Chang CH, Hsu CF, et al. Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence. Br J Pharmacol 2020; 177(6): 1409-23.
[http://dx.doi.org/10.1111/bph.14816] [PMID: 31368509]
[3]
Lin S-R, Fu Y-S, Tsai M-J, Cheng H, Weng C-F. Natural compounds from herbs that can potentially execute as autophagy inducers for cancer therapy. Int J Mol Sci 2017; 18(7): 1412.
[http://dx.doi.org/10.3390/ijms18071412] [PMID: 28671583]
[4]
Zhou Y, Zheng J, Li Y, et al. Natural polyphenols for prevention and treatment of cancer. Nutrients 2016; 8(8): 515.
[http://dx.doi.org/10.3390/nu8080515] [PMID: 27556486]
[5]
Talib WH. A ketogenic diet combined with melatonin overcomes cisplatin and vincristine drug resistance in breast carcinoma syngraft. Nutrition 2020; 72: 110659.
[http://dx.doi.org/10.1016/j.nut.2019.110659] [PMID: 31986320]
[6]
Talib WH. Regressions of breast carcinoma syngraft following treatment with piperine in combination with thymoquinone. Sci Pharm 2017; 85(3): 27.
[http://dx.doi.org/10.3390/scipharm85030027] [PMID: 28671634]
[7]
Qingming Y, Xianhui P, Weibao K, et al. Antioxidant activities of malt extract from barley (Hordeum vulgare L.) toward various oxidative stress in vitro and in vivo. Food Chem 2010; 118(1): 84-9.
[http://dx.doi.org/10.1016/j.foodchem.2009.04.094]
[8]
Talib WH, Al-Hadid SA, Ali MBW, Al-Yasari IH, Ali MRA. Role of curcumin in regulating p53 in breast cancer: An overview of the mechanism of action. Breast Cancer (Dove Med Press) 2018; 10: 207-17.
[http://dx.doi.org/10.2147/BCTT.S167812] [PMID: 30568488]
[9]
Thoppil RJ, Bhatia D, Barnes KF, et al. Black currant anthocyanins abrogate oxidative stress through Nrf2- mediated antioxidant mecha-nisms in a rat model of hepatocellular carcinoma. Curr Cancer Drug Targets 2012; 12(9): 1244-57.
[PMID: 22873220]
[10]
Ren M, Ye L, Hao X, et al. Polysaccharides from Tricholoma matsutake and Lentinus edodes enhance 5-fluorouracil-mediated H22 cell growth inhibition. J Tradit Chin Med 2014; 34(3): 309-16.
[http://dx.doi.org/10.1016/S0254-6272(14)60095-9] [PMID: 24992758]
[11]
Yu MH, Gwon Im H, Gyu Lee S, Kim D-I, Jeong Seo H, Lee I-S. Inhibitory effect of immature plum on PMA-induced MMP-9 expression in human hepatocellular carcinoma. Nat Prod Res 2009; 23(8): 704-18.
[http://dx.doi.org/10.1080/14786410802263485] [PMID: 19418353]
[12]
Nikolić M, Glamočlija J, Ferreira IC, et al. Chemical composition, antimicrobial, antioxidant and antitumor activity of Thymus serpyllum L., Thymus algeriensis Boiss. and Reut and Thymus vulgaris L. essential oils. Ind Crops Prod 2014; 52: 183-90.
[http://dx.doi.org/10.1016/j.indcrop.2013.10.006]
[13]
Chauhan AK, Jakhar R, Paul S, Kang SC. Potentiation of macrophage activity by thymol through augmenting phagocytosis. Int Immunopharmacol 2014; 18(2): 340-6.
[http://dx.doi.org/10.1016/j.intimp.2013.11.025] [PMID: 24316253]
[14]
Kulisić T, Kriško A, Dragović-Uzelac V, Miloš M, Pifat G. The effects of essential oils and aqueous tea infusions of oregano (Origanum vulgare L. spp. hirtum), thyme (Thymus vulgaris L.) and wild thyme (Thymus serpyllum L.) on the copper-induced oxidation of human low-density lipoproteins. Int J Food Sci Nutr 2007; 58(2): 87-93.
[http://dx.doi.org/10.1080/09637480601108307] [PMID: 17469764]
[15]
Cao W, Mo K, Wei S, Lan X, Zhang W, Jiang W. Effects of rosmarinic acid on immunoregulatory activity and hepatocellular carcinoma cell apoptosis in H22 tumor-bearing mice. Korean J Physiol Pharmacol 2019; 23(6): 501-8.
[http://dx.doi.org/10.4196/kjpp.2019.23.6.501] [PMID: 31680772]
[16]
Petersen M, Simmonds MS. Rosmarinic acid. Phytochemistry 2003; 62(2): 121-5.
[http://dx.doi.org/10.1016/S0031-9422(02)00513-7] [PMID: 12482446]
[17]
Al-Awaida W, Al-Hourani BJ, Akash M, et al. In vitro anticancer, anti-inflammatory, and antioxidant potentials of Ephedra aphylla. J Cancer Res Ther 2018; 14(6): 1350-4.
[http://dx.doi.org/10.4103/0973-1482.196760] [PMID: 30488855]
[18]
Talib WH, Mahasneh AM. Combination of Ononis hirta and bifidobacterium longum decreases syngeneic mouse mammary tumor burden and enhances immune response. J Cancer Res Ther 2012; 8(3): 417-23.
[http://dx.doi.org/10.4103/0973-1482.103523] [PMID: 23174725]
[19]
Talib WH, Al Kury LT. Parthenolide inhibits tumor-promoting effects of nicotine in lung cancer by inducing P53 - dependent apoptosis and inhibiting VEGF expression. Biomed Pharmacother 2018; 107: 1488-95.
[http://dx.doi.org/10.1016/j.biopha.2018.08.139] [PMID: 30257366]
[20]
Faustino-Rocha A, Oliveira PA, Pinho-Oliveira J, et al. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. Lab Anim (NY) 2013; 42(6): 217-24.
[http://dx.doi.org/10.1038/laban.254] [PMID: 23689461]
[21]
Mahmod AI, Talib WH. Anticancer activity of mandragora autumnalis: An in vitro and in vivo study. Pharmacia 2021; 68(4): 827-36.
[http://dx.doi.org/10.3897/pharmacia.68.e71695]
[22]
Chen J-R, Yang Z-Q, Hu T-J, et al. Immunomodulatory activity in vitro and in vivo of polysaccharide from Potentilla anserina. Fitoterapia 2010; 81(8): 1117-24.
[http://dx.doi.org/10.1016/j.fitote.2010.07.009] [PMID: 20624446]
[23]
Ray A, Dittel BN. Isolation of mouse peritoneal cavity cells. J Vis Exp 2010; (35): 1488.
[PMID: 20110936]
[24]
Al Obaydi MF, Hamed WM, Al Kury LT, Talib WH. Terfezia boudieri: A desert truffle with anticancer and immunomodulatory activities. Front Nutr 2020; 7(10): 38.
[http://dx.doi.org/10.3389/fnut.2020.00038] [PMID: 32322585]
[25]
Boothapandi M, Ramanibai R. Immunomodulatory activity of Indigofera tinctoria leaf extract on in vitro macrophage responses and lym-phocyte proliferation. Int J Pharm Pharm Sci 2016; 8: 58-63.
[26]
Kury LTA, Taha Z, Talib WH. Immunomodulatory and anticancer activities of Hyacinthus orientalis L.: An in vitro and in vivo study. Plants 2021; 10(4): 617.
[http://dx.doi.org/10.3390/plants10040617] [PMID: 33805000]
[27]
Mir MA, Sawhney S, Jassal M. Qualitative and quantitative analysis of phytochemicals of Taraxacum officinale. Wudpecker J Pharm Pharmocol 2013; 2(1): 1-5.
[28]
Baig S, Ahmad BA, Azizan AHS, Ali HM, Rouhollahi E, Abdulla MA. Hexane Extract of Thymus serpyllum L.: GC-MS profile, antioxidant potential and anticancer impact on HepG2 (liver carcinoma) cell line. Int Sci Index 2014; 8: 1518-25.
[29]
Ma Z, Yang J, Yang Y, et al. Rosmarinic acid exerts an anticancer effect on osteosarcoma cells by inhibiting DJ-1 via regulation of the PTEN-PI3K-Akt signaling pathway. Phytomedicine 2020; 68: 153186.
[http://dx.doi.org/10.1016/j.phymed.2020.153186] [PMID: 32088353]
[30]
Liao XZ, Gao Y, Sun LL, et al. Rosmarinic acid reverses non-small cell lung cancer cisplatin resistance by activating the MAPK signaling pathway. Phytother Res 2020; 34(5): 1142-53.
[http://dx.doi.org/10.1002/ptr.6584] [PMID: 31985119]
[31]
Han Y-H, Kee J-Y, Hong S-H. Rosmarinic acid activates AMPK to inhibit metastasis of colorectal cancer. Front Pharmacol 2018; 9: 68.
[http://dx.doi.org/10.3389/fphar.2018.00068] [PMID: 29459827]
[32]
Baranauskaite J, Kubiliene A, Marksa M, et al. The influence of different oregano species on the antioxidant activity determined using hplc postcolumn DPPH method and anticancer activity of carvacrol and rosmarinic acid. BioMed Res Int 2017; 2017: 1681392.
[http://dx.doi.org/10.1155/2017/1681392] [PMID: 29181386]
[33]
Pakdemirli A, Karaca C, Sever T, et al. Carvacrol alters soluble factors in HCT-116 and HT-29 cell lines. Turk J Med Sci 2020; 50(1): 271-6.
[PMID: 31742371]
[34]
Chauhan AK, Bahuguna A, Paul S, Kang SC. Thymol elicits HCT-116 colorectal carcinoma cell death through induction of oxidative stress. Anticancer Agents Med Chem 2017; 17(14): 1942-50.
[35]
Seresht HR, Albadry BJ, Al-mosawi AKM, Gholami O, Cheshomi H. The cytotoxic effects of thymol as the major component of tra-chyspermum ammi on breast cancer (MCF-7) cells. Pharm Chem J 2019; 53(2): 101-7.
[http://dx.doi.org/10.1007/s11094-019-01961-w]
[36]
Mander S, Kim DH, Nguyen HT, et al. SP-8356, a (1S)-(–)-verbenone derivative, exerts in vitro and in vivo anti-breast cancer effects by inhibiting NF-κB signaling. Sci Rep 2019; 9(1): 1-11.
[http://dx.doi.org/10.1038/s41598-019-41224-y] [PMID: 30626917]
[37]
Zhang W, Tang B, Huang Q, Hua Z. Galangin inhibits tumor growth and metastasis of B16F10 melanoma. J Cell Biochem 2013; 114(1): 152-61.
[http://dx.doi.org/10.1002/jcb.24312] [PMID: 22887049]
[38]
Roohbakhsh A, Parhiz H, Soltani F, Rezaee R, Iranshahi M. Molecular mechanisms behind the biological effects of hesperidin and hes-peretin for the prevention of cancer and cardiovascular diseases. Life Sci 2015; 124: 64-74.
[http://dx.doi.org/10.1016/j.lfs.2014.12.030] [PMID: 25625242]
[39]
Saleem U, Bashir A, Mobasher A, Hussain K, Bukhari NI, Anjum AA. Determination of cytotoxicity of latex and methanol extract of Eu-phorbia helioscopia leaves on vero cell line with MTT assay. Pak J Zool 2014; 46(3): 741-5.
[40]
Patel S, Gheewala N, Suthar A, Shah A. In-vitro cytotoxicity activity of Solanum nigrum extract against Hela cell line and Vero cell line. Int J Pharm Pharm Sci 2009; 1(1): 38-46.
[41]
Elaimy AL, Mercurio AM. Convergence of VEGF and YAP/TAZ signaling: Implications for angiogenesis and cancer biology. Sci Signal 2018; 11(552): eaau1165.
[http://dx.doi.org/10.1126/scisignal.aau1165] [PMID: 30327408]
[42]
Cao W, Hu C, Wu L, Xu L, Jiang W. Rosmarinic acid inhibits inflammation and angiogenesis of hepatocellular carcinoma by suppression of NF-κB signaling in H22 tumor-bearing mice. J Pharmacol Sci 2016; 132(2): 131-7.
[http://dx.doi.org/10.1016/j.jphs.2016.09.003] [PMID: 27707649]
[43]
Matluobi D, Araghi A, Maragheh BFA, et al. Carvacrol promotes angiogenic paracrine potential and endothelial differentiation of human mesenchymal stem cells at low concentrations. Microvasc Res 2018; 115: 20-7.
[http://dx.doi.org/10.1016/j.mvr.2017.08.003] [PMID: 28830763]
[44]
Huang H, Chen AY, Rojanasakul Y, Ye X, Rankin GO, Chen YC. Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis. J Funct Foods 2015; 15: 464-75.
[http://dx.doi.org/10.1016/j.jff.2015.03.051] [PMID: 26113875]
[45]
Hana RS, Bawi BL. Hesperidin inhibits angiogenesis, induces apoptosis, and suppresses laryngeal cancer cell metastasis. Ibnosina J Med Biomed Sci 2018; 10(5): 169.
[http://dx.doi.org/10.4103/ijmbs.ijmbs_21_18]
[46]
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011; 144(5): 646-74.
[47]
Sharmila R, Manoharan S. Anti-tumor activity of rosmarinic acid in 7, 12-dimethylbenz (a) anthracene (DMBA) induced skin carcinogenesis in Swiss albino mice. 2012; 50: 187.: 94.
[48]
Yin QH, Yan FX, Zu X-Y, et al. Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2. Cytotechnology 2012; 64(1): 43-51.
[http://dx.doi.org/10.1007/s10616-011-9389-y] [PMID: 21938469]
[49]
Deb DD, Parimala G, Saravana Devi S, Chakraborty T. Effect of thymol on peripheral blood mononuclear cell PBMC and acute promy-elotic cancer cell line HL-60. Chem Biol Interact 2011; 193(1): 97-106.
[http://dx.doi.org/10.1016/j.cbi.2011.05.009] [PMID: 21640085]
[50]
Xia R, Sheng X, Xu X, Yu C, Lu H. Hesperidin induces apoptosis and G0/G1 arrest in human non-small cell lung cancer A549 cells. Int J Mol Med 2018; 41(1): 464-72.
[PMID: 29138795]
[51]
Kong Y, Feng Z, Chen A, et al. The natural flavonoid galangin elicits apoptosis, pyroptosis, and autophagy in glioblastoma. Front Oncol 2019; 9: 942.
[http://dx.doi.org/10.3389/fonc.2019.00942] [PMID: 31612107]
[52]
Chkhikvishvili I, Sanikidze T, Gogia N, et al. Rosmarinic acid-rich extracts of summer savory (Satureja hortensis L.) protect Jurkat T cells against oxidative stress. Oxid Med Cell Longev 2013; 2013: 456253.
[http://dx.doi.org/10.1155/2013/456253] [PMID: 24349613]
[53]
Chan AS, Pang H, Yip EC, Tam YK, Wong YH. Carvacrol and eugenol differentially stimulate intracellular Ca2+ mobilization and mitogen-activated protein kinases in Jurkat T-cells and monocytic THP-1 cells. Planta Med 2005; 71(7): 634-9.
[http://dx.doi.org/10.1055/s-2005-871269] [PMID: 16041649]
[54]
Gholijani N, Gharagozloo M, Kalantar F, Ramezani A, Amirghofran Z. Modulation of cytokine production and transcription factors activi-ties in human jurkat T cells by thymol and carvacrol. Adv Pharm Bull 2015; 5 (Suppl. 1): 653-60.
[http://dx.doi.org/10.15171/apb.2015.089] [PMID: 26793612]
[55]
Al-Abd NM, Kassim M, Zajmi A. The inhibitory effect of GALANGIN on cytokines and nitric oxide in microglia BV2 cell line. Malays J Sci Ser B Phys Earth Sci 2017; 36(3): 145-56.
[http://dx.doi.org/10.22452/mjs.vol36no3.2]
[56]
Somensi N, Rabelo TK, Guimarães AG, et al. Carvacrol suppresses LPS-induced pro-inflammatory activation in RAW 264.7 macrophages through ERK1/2 and NF-kB pathway. Int Immunopharmacol 2019; 75: 105743.
[http://dx.doi.org/10.1016/j.intimp.2019.105743] [PMID: 31357087]
[57]
Volpatti D, Chiara B, Francesca T, Marco G. Growth parameters, innate immune response and resistance to L istonella (V ibrio) anguilla-rum of D icentrarchus labrax fed carvacrol supplemented diets. Aquacult Res 2013; 45(1): 31-44.
[http://dx.doi.org/10.1111/j.1365-2109.2012.03202.x]
[58]
Liu RH. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr 2003; 78(3) (Suppl.): 517S-20S.
[http://dx.doi.org/10.1093/ajcn/78.3.517S] [PMID: 12936943]
[59]
Karna P, Chagani S, Gundala SR, et al. Benefits of whole ginger extract in prostate cancer. Br J Nutr 2012; 107(4): 473-84.
[http://dx.doi.org/10.1017/S0007114511003308] [PMID: 21849094]
[60]
Kubatka P, Uramova S, Kello M, et al. Anticancer activities of Thymus vulgaris L. in experimental breast carcinoma in vivo and in vitro. Int J Mol Sci 2019; 20(7): 1749.
[http://dx.doi.org/10.3390/ijms20071749] [PMID: 30970626]
[61]
Khan I, Bahuguna A, Kumar P, Bajpai VK, Kang SC. In vitro and in vivo antitumor potential of carvacrol nanoemulsion against human lung adenocarcinoma A549 cells via mitochondrial mediated apoptosis. Sci Rep 2018; 8(1): 144.
[http://dx.doi.org/10.1038/s41598-017-18644-9] [PMID: 29317755]
[62]
Ahmed HH, Shousha WG, El-Mezayen H, Ismaiel NN, Mahmoud NS. In vivo antitumor potential of carvacerol against hepatocellular car-cinoma in rat moderl. World J Pharm Pharm Sci 2013; 2(5): 2367-96.
[63]
Zhu L, Luo Q, Bi J, Ding J, Ge S, Chen F. Galangin inhibits growth of human head and neck squamous carcinoma cells in vitro and in vivo. Chem Biol Interact 2014; 224: 149-56.
[http://dx.doi.org/10.1016/j.cbi.2014.10.027] [PMID: 25450235]
[64]
Daferera DJ, Ziogas BN, Polissiou MG. GC-MS analysis of essential oils from some Greek aromatic plants and their fungitoxicity on Pen-icillium digitatum. J Agric Food Chem 2000; 48(6): 2576-81.
[http://dx.doi.org/10.1021/jf990835x] [PMID: 10888587]
[65]
Venskutonis P. Effect of drying on the volatile constituents of thyme (Thymus vulgaris L.) and sage (Salvia officinalis L.). Food Chem 1997; 59(2): 219-27.
[http://dx.doi.org/10.1016/S0308-8146(96)00242-7]
[66]
Bozin B, Mimica-Dukic N, Simin N, Anackov G. Characterization of the volatile composition of essential oils of some lamiaceae spices and the antimicrobial and antioxidant activities of the entire oils. J Agric Food Chem 2006; 54(5): 1822-8.
[http://dx.doi.org/10.1021/jf051922u] [PMID: 16506839]
[67]
Proestos C, Sereli D, Komaitis M. Determination of phenolic compounds in aromatic plants by RP-HPLC and GC-MS. Food Chem 2006; 95(1): 44-52.
[http://dx.doi.org/10.1016/j.foodchem.2004.12.016]

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