Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

Research Article

Eryngium billardieri Extract and Fractions Induce Apoptosis in Cancerous Cells

Author(s): Samira Hasanbeiglu, Kamran Hosseini, Ommoleila Molavi, Parina Asgharian* and Vahideh Tarhriz*

Volume 22, Issue 11, 2022

Published on: 24 January, 2022

Page: [2189 - 2201] Pages: 13

DOI: 10.2174/1871520621666211201151736

Price: $65

Abstract

Background: Eryngium is a genus flowering plant in the Umbelliferae family, having pharmacological properties, such as anti-inflammatory and anti-diabetic. Given the nature of melanoma and breast cancers in recent years and the fact that the anti-cancer properties of Eryngium billardieri on mentioned cell lines have not been studied, the present study was conducted to explore these properties.

Objective: The mechanisms of cytotoxicity and apoptosis of aerial parts of various extracts and fractions of E. billardieri on cancerous cells and normal cells were investigated.

Methods: Samples were collected from natural habitats, dried and then extracted by Soxhlet apparatus with solvents of n-Hex, DCM and methanol, respectively. The cytotoxic effects of the extracts were investigated by the MTT method on MCF7, B16 and HFF-2 classes for 24 and 48 hours. Flow cytometry was also used to investigate the mechanism of cytotoxicity, and it has been confirmed by Real-time PCR of p53 and Bax genes as to which comprise the apoptosis regulatory proteins. Meanwhile, volatile compounds of extracts were identified by the GC-MS method.

Results: The obtained data showed that the n-Hex extract of E. billardieri on B-16 and MCF7 cell lines and dichromethane extract on MCF7 cell line had the most significant cytotoxic effect compared to DMSO control (p-value <0.001). Our finding showed that the mechanism of n-Hex extract with 80% and 100% vlc fractions on B16 induced apoptotis compared to HFF-2 control cells; moreover, n-Hex extract and 80% vlc fraction on MCF7 were apoptotic. The major compounds of n-Hex, DCM, and 80% and 100% fractions of n-Hex extract obtained from GC-MS were non-terpenoid.

Conclusion: Non-terpenoid compounds of E. billardieri can be responsible for exhibiting the most cytotoxic effects on MCF7 and B16 cell lines with apoptotic mechanism, and n-Hex extract was found to have the most significant inhibitory effect on cancerous cells compared to the HFF-2 control cells by employing the mechanism of apoptosis.

Keywords: Eryngium billardieri, cancer, apoptosis, flow cytometry, GC-MS, cytotoxic effects.

« Previous
Graphical Abstract

[1]
Miller, K.D.; Siegel, R.L.; Lin, C.C.; Mariotto, A.B.; Kramer, J.L.; Rowland, J.H.; Stein, K.D.; Alteri, R.; Jemal, A. Cancer treatment and survivorship statistics. CA Cancer J. Clin., 2016, 66(4), 271-289.
[http://dx.doi.org/10.3322/caac.21349] [PMID: 27253694]
[2]
Zarei, A.; Ashtiyani, S.C.; Hamidizadeh, S.; Rezaei, A. The study of the effects hydro-alcoholic extract of Eryngium billardieri on lipid profiles levels and liver and renal functions tests in hypercholesterolemic rats. Glob. J. Pharmacol., 2015, 9(1), 21-27.
[http://dx.doi.org/10.5829/idosi.gjp.2015.9.1.91137]
[3]
Miller, K.D.; Fidler-Benaoudia, M.; Keegan, T.H.; Hipp, H.S.; Jemal, A.; Siegel, R.L. Cancer statistics for adolescents and young adults, 2020. CA Cancer J. Clin., 2020, 70(6), 443-459.
[http://dx.doi.org/10.3322/caac.21637] [PMID: 32940362]
[4]
Key, T.J.; Verkasalo, P.K.; Banks, E. Epidemiology of breast cancer. Lancet Oncol., 2001, 2(3), 133-140.
[http://dx.doi.org/10.1016/S1470-2045(00)00254-0] [PMID: 11902563]
[5]
Bernstein, L.; Ross, R.K. Endogenous hormones and breast cancer risk. Epidemiol. Rev., 1993, 15(1), 48-65.
[http://dx.doi.org/10.1093/oxfordjournals.epirev.a036116] [PMID: 8405212]
[6]
Leiter, U.; Garbe, C. Epidemiology of melanoma and nonmelanoma skin cancer-the role of sunlight. Adv. Exp. Med. Biol., 2008, 624, 89-103.
[http://dx.doi.org/10.1007/978-0-387-77574-6_8] [PMID: 18348450]
[7]
Payandeh, Z.; Yarahmadi, M.; Nariman-Saleh-Fam, Z.; Tarhriz, V.; Islami, M.; Aghdam, A.M.; Eyvazi, S. Immune therapy of melanoma: Overview of therapeutic vaccines. J. Cell. Physiol., 2019, 234(9), 14612-14621.
[http://dx.doi.org/10.1002/jcp.28181] [PMID: 30706472]
[8]
Anand, P.; Kunnumakkara, A.B.; Sundaram, C.; Harikumar, K.B.; Tharakan, S.T.; Lai, O.S.; Sung, B.; Aggarwal, B.B. Cancer is a preventable disease that requires major lifestyle changes. Pharm. Res., 2008, 25(9), 2097-2116.
[http://dx.doi.org/10.1007/s11095-008-9661-9] [PMID: 18626751]
[9]
Miller, K.D.; Siegel, R.L.; Lin, C.C.; Mariotto, A.B.; Kramer, J.L.; Rowland, J.H.; Stein, K.D.; Alteri, R.; Jemal, A. Cancer treatment and survivorship statistics, 2016. CA Cancer J. Clin., 2016, 66(4), 271-289.
[http://dx.doi.org/10.3322/caac.21349] [PMID: 27253694]
[10]
Fathi, E.; Sanaat, Z.; Farahzadi, R. Mesenchymal stem cells in acute myeloid leukemia: A focus on mechanisms involved and therapeutic concepts. Blood Res., 2019, 54(3), 165-174.
[http://dx.doi.org/10.5045/br.2019.54.3.165] [PMID: 31730689]
[11]
Harvey, A.L. Natural products in drug discovery. Drug Discov. Today, 2008, 13(19-20), 894-901.
[http://dx.doi.org/10.1016/j.drudis.2008.07.004] [PMID: 18691670]
[12]
Khazir, J.; Mir, B.A.; Pilcher, L.; Riley, D.L. Role of plants in anticancer drug discovery. Phytochem. Lett., 2014, 7, 173-181.
[http://dx.doi.org/10.1016/j.phytol.2013.11.010]
[13]
Bagheri, Y.; Fathi, E.; Maghoul, A.; Moshtagh, S.; Mokhtari, K.; Abdollahpour, A.; Montazersaheb, S.; Bagheri, A. Effects of Achillea tenuifolia Lam. hydro-alcoholic extract on anxiety-like behavior and reproductive parameters in rat model of chronic restraint stress. Hum. Exp. Toxicol., 2021., 9603271211026723.
[http://dx.doi.org/10.1177/09603271211026723] [PMID: 34167364]
[14]
Bagheri, Y.; Barati, A.; Nouraei, S.; Jalili Namini, N.; Bakhshi, M.; Fathi, E.; Montazersaheb, S. Comparative study of gavage and intraperitoneal administration of gamma-oryzanol in alleviation/attenuation in a rat animal model of renal ischemia/reperfusion-induced injury. Iran. J. Basic Med. Sci., 2021, 24(2), 175-183.
[http://dx.doi.org/10.22038/IJBMS.2020.51276.11642] [PMID: 33953856]
[15]
Al-Snafi, A.E. Chemical constituents and pharmacological effects of Eryngium creticum -A review. Indo Am. J. Pharm. Sci., 2017, 4(1), 67-73.
[http://dx.doi.org/10.5281/zenodo.268946]
[16]
Wang, P.; Su, Z.; Yuan, W.; Deng, G.; Li, S. Phytochemical constituents and pharmacological activities of Eryngium L. (Apiaceae). Pharm. Crops, 2012, 3, 99-120.
[http://dx.doi.org/10.2174/2210290601203010099]
[17]
El Dirani, Z.; Makki, R.; Rammal, H.; Naserddine, S.; Hijazi, A.; Kazan, H.F.; Nasser, M.; Daher, A.; Badran, B. The antioxidant and anti-tumor activities of the Lebanese Eryngium creticum L. Int. J. Biol. Pharm. Allied Sci., 2014, 3(10), 2199-2222.
[18]
Khader, M.; Bresgen, N.; Eckl, P.M. Antimutagenic effects of ethanolic extracts from selected Palestinian medicinal plants. J. Ethnopharmacol., 2010, 127(2), 319-324.
[http://dx.doi.org/10.1016/j.jep.2009.11.001] [PMID: 19913082]
[19]
Targett, N.M.; Kilcoyne, J.; Green, B. Vacuum liquid chromatography: An alternative to common chromatographic methods. J. Org. Chem., 1979, 44(26), 4962-4964.
[http://dx.doi.org/10.1021/jo00394a045]
[20]
Maurya, A.; Kalani, K.; Verma, S.C.; Singh, R.; Srivastava, A. Vacuum liquid chromatography: simple, efficient and versatile separation technique for natural products. Org Med Chem IJ., 2018, 7(2), 1-3.
[http://dx.doi.org/10.19080/OMCIJ.2018.07.555710]
[21]
Fathi, E.; Valipour, B.; Farahzadi, R. Targeting the proliferation inhibition of chronic myeloid leukemia cells by bone marrow derived-mesenchymal stem cells via ERK pathway as a therapeutic strategy. Acta Med. Iran., 2020, 58(5), 199-206.
[http://dx.doi.org/10.18502/acta.v58i5.3952]
[22]
Montazersaheb, S.; Avci, Ç.B.; Bagca, B.G.; Ay, N.P.O.; Tarhriz, V.; Nielsen, P.E.; Charoudeh, H.N.; Hejazi, M.S. Targeting TdT gene expression in Molt-4 cells by PNA-octaarginine conjugates. Int. J. Biol. Macromol., 2020, 164, 4583-4590.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.09.081] [PMID: 32941907]
[23]
Ferrari, M.; Fornasiero, M.C.; Isetta, A.M. MTT colorimetric assay for testing macrophage cytotoxic activity in vitro. J. Immunol. Methods, 1990, 131(2), 165-172.
[http://dx.doi.org/10.1016/0022-1759(90)90187-Z] [PMID: 2391427]
[24]
Tarhriz, V.; Wagner, K.D.; Masoumi, Z.; Molavi, O.; Hejazi, M.S.; Ghanbarian, H. CDK9 regulates apoptosis of myoblast cells by modulation of microRNA‐1 expression. J. Cell. Biochem., 2018, 119(1), 547-554.
[http://dx.doi.org/10.1002/jcb.26213] [PMID: 28608935]
[25]
Fathi, E.; Farahzadi, R.; Javanmardi, S.; Vietor, I. L-carnitine extends the telomere length of the cardiac differentiated CD117+- expressing stem cells. Tissue Cell, 2020, 67, 101429.
[http://dx.doi.org/10.1016/j.tice.2020.101429] [PMID: 32861877]
[26]
Montazersaheb, S.; Kabiri, F.; Saliani, N.; Nourazarian, A.; Avci, Ç.B.; Rahbarghazi, R.; Nozad Charoudeh, H. Prolonged incubation with metformin decreased angiogenic potential in human bone marrow mesenchymal stem cells. Biomed. Pharmacother., 2018, 108, 1328-1337.
[http://dx.doi.org/10.1016/j.biopha.2018.09.135] [PMID: 30372835]
[27]
Fathi, E.; Farahzadi, R.; Valipour, B. Alginate/gelatin encapsulation promotes NK cells differentiation potential of bone marrow resident C-kit+ hematopoietic stem cells. Int. J. Biol. Macromol., 2021, 177, 317-327.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.02.131] [PMID: 33621568]
[28]
Montazersaheb, S.; Kazemi, M.; Nabat, E.; Nielsen, P.E.; Hejazi, M.S. Downregulation of TdT expression through splicing modulation by antisense peptide nucleic acid (PNA). Curr. Pharm. Biotechnol., 2019, 20(2), 168-178.
[http://dx.doi.org/10.2174/1389201020666190206202650] [PMID: 30727883]
[29]
Tarhriz, V.; Eyvazi, S.; Musavi, M.; Abasi, M.; Sharifi, K.; Ghanbarian, H.; Hejazi, M.S. Transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis. J. Cell. Biochem., 2019, 120(11), 18854-18861.
[http://dx.doi.org/10.1002/jcb.29204] [PMID: 31257635]
[30]
Mazrouei, R.; Raeisi, E.; Lemoigne, Y.; Heidarian, E. Activation of p53 gene expression and synergistic antiproliferative effects of 5-fluorouracil and β-escin on MCF7 cells. J. Med. Signals Sens., 2019, 9(3), 196-203.
[http://dx.doi.org/10.4103/jmss.JMSS_44_18] [PMID: 31544060]
[31]
Zhou, X-Q.; Li, Y.; Zhang, D-Y.; Nie, Y.; Li, Z-J.; Gu, W.; Liu, X.; Tian, J.L.; Yan, S.P. Copper complexes based on chiral Schiff-base ligands: DNA/BSA binding ability, DNA cleavage activity, cytotoxicity and mechanism of apoptosis. Eur. J. Med. Chem., 2016, 114, 244-256.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.055] [PMID: 26994692]
[32]
Ghatei, N.; Nabavi, A.S.; Toosi, M.H.B.; Azimian, H.; Homayoun, M.; Targhi, R.G.; Haghir, H. Evaluation of bax, bcl-2, p21 and p53 genes expression variations on cerebellum of BALB/c mice before and after birth under mobile phone radiation exposure. Iran. J. Basic Med. Sci., 2017, 20(9), 1037-1043.
[http://dx.doi.org/10.22038/IJBMS.2017.9273] [PMID: 29085599]
[33]
Fathi, E.; Farahzadi, R.; Vietor, I.; Javanmardi, S. Cardiac differentiation of bone-marrow-resident c-kit+ stem cells by L-carnitine increases through secretion of VEGF, IL6, IGF-1, and TGF- β as clinical agents in cardiac regeneration. J. Biosci., 2020, 45(1), 1-11.
[http://dx.doi.org/10.1007/s12038-020-00063-0] [PMID: 32713855]
[34]
Ninfa, A.J.; Ballou, D.P.; Benore, M. Fundamental laboratory approaches for biochemistry and biotechnology; John Wiley & Sons, 2009.
[35]
Fathi, E.; Vietor, I. Mesenchymal stem cells promote caspase expression in Molt-4 leukemia cells Via GSK-3α/B and ERK1/2 signaling pathways as a therapeutic strategy. Curr. Gene Ther., 2021, 21(1), 81-88.
[http://dx.doi.org/10.2174/1566523220666201005111126] [PMID: 33019931]
[36]
do Nascimento, K.F.; Moreira, F.M.F.; Alencar Santos, J.; Kassuya, C.A.L.; Croda, J.H.R.; Cardoso, C.A.L.; Vieira, M.D.C.; Góis Ruiz, A.L.T.; Ann Foglio, M.; de Carvalho, J.E.; Formagio, A.S.N. Antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of Psidium guineense Sw. and spathulenol. J. Ethnopharmacol., 2018, 210, 351-358.
[http://dx.doi.org/10.1016/j.jep.2017.08.030] [PMID: 28844678]
[37]
Aparna, V.; Dileep, K.V.; Mandal, P.K.; Karthe, P.; Sadasivan, C.; Haridas, M. Anti-inflammatory property of n-hexadecanoic acid: Structural evidence and kinetic assessment. Chem. Biol. Drug Des., 2012, 80(3), 434-439.
[http://dx.doi.org/10.1111/j.1747-0285.2012.01418.x] [PMID: 22642495]
[38]
Kumar, P.P.; Kumaravel, S.; Lalitha, C. Screening of antioxidant activity, total phenolics and GC-MS study of Vitex negundo. Afr. J. Biochem. Res., 2010, 4(7), 191-195.
[http://dx.doi.org/10.5897/AJBR.9000213]
[39]
Chandrasekaran, M.; Senthilkumar, A.; Venkatesalu, V. Antibacterial and antifungal efficacy of fatty acid methyl esters from the leaves of Sesuvium portulacastrum L. Eur. Rev. Med. Pharmacol. Sci., 2011, 15(7), 775-780.
[PMID: 21780546]
[40]
Yerer, M.B.; Bishayee, A. Report on second international conference on natural products for cancer prevention and therapy held in Kayseri, Turkey, 8-11 November 2017. Nutrients, 2017, 10(1), 8.
[http://dx.doi.org/10.3390/nu10010008] [PMID: 29295493]
[41]
Kardan, M.; Yazdani, Z.; Morsaljahan, Z.; Ebrahimzadeh, M.A.; Rafiei, A. Cytotoxic effect of methanolic extracts of Fritillaria imperialis bulbs and Eryngium caucasicum leaves on hepatoma and colon cancer cells. Asian Pac. J. Trop. Biomed., 2019, 9(8), 353.
[http://dx.doi.org/10.4103/2221-1691.262084]
[42]
Roshanravan, N.; Asgharian, P.; Dariushnejad, H.; Mesri Alamdari, N.; Mansoori, B.; Mohammadi, A.; Alipour, S.; Barati, M.; Ghavami, A.; Ghorbanzadeh, V.; Aamazadeh, F.; Ostadrahimi, A. Eryngium billardieri induces apoptosis via bax gene expression in pancreatic cancer cells. Adv. Pharm. Bull., 2018, 8(4), 667-674.
[http://dx.doi.org/10.15171/apb.2018.075] [PMID: 30607339]
[43]
Vukic, M.D.; Vukovic, N.L.; Djelic, G.T.; Obradovic, A.; Kacaniova, M.M.; Markovic, S. Phytochemical analysis, antioxidant, antibacterial and cytotoxic activity of different plant organs of Eryngium serbicum L. Ind. Crops Prod., 2018, 115, 88-97.
[http://dx.doi.org/10.1016/j.indcrop.2018.02.031]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy