Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Cytotoxicity of Anchusa arvensis Against HepG-2 Cell Lines: Mechanistic and Computational Approaches

Author(s): Sajid Hussain *, Farhat Ullah, Abdul Sadiq , Muhammad Ayaz , Azhar-ul-Haq Ali Shah, Syed Adnan Ali Shah , Syed Majid Shah , Akhtar Nadhman, Farman Ullah , Abdul Wadood and Mohamed El-Shazly

Volume 19, Issue 30, 2019

Page: [2805 - 2813] Pages: 9

DOI: 10.2174/1568026619666191105103801

Price: $65

Abstract

Background: Liver cancer is a devastating cancer with increasing incidence and mortality rates worldwide. Plants possess numerous therapeutic properties, therefore the search for novel, naturally occurring cytotoxic compounds is urgently needed.

Methods: The anticancer activity of plant extracts and isolated compounds from Anchusa arvensis (A. arvensis) were studied against the cell culture of HepG-2 (human hepatocellular carcinoma cell lines) using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. Apoptosis was investigated by performing Acridine orange –ethidium bromide staining, styox green assay and DNA interaction study. We also used tools for computational chemistry studies of isolated compounds with the tyrosine kinase.

Results: In MTT assay, the crude extract caused a significant cytotoxic effect with IC50 of 34.14 ± 0.9 μg/ml against HepG-2 cell lines. Upon fractionation, chloroform fraction (Aa.Chm) exhibited the highest antiproliferative activity with IC50 6.55 ± 1.2 μg/ml followed by ethyl acetate (Aa.Et) fraction (IC50, 24.59 ± 0.85 μg/ml) and n-hexane (Aa.Hex) fraction (IC50 29.53 ± 1.5μg/ml). However, the aqueous (Aa.Aq) fraction did not show any anti-proliferative activity. Bioactivity-guided isolation led to the isolation of two compounds which were characterized as para–methoxycatechol (1) and decane (2) through various spectroscopic techniques. Against HepG-2 cells, compound 1 showed marked potency with IC50 6.03 ± 0.75 μg/ml followed by 2 with IC50 18.52 ± 1.9 μg/ml. DMSO was used as a negative control and doxorubicin as a reference standard (IC50 1.3 ± 0.21 μg/ml). It was observed that compounds 1-2 caused apoptotic cell death evaluated by Acridine orange –ethidium bromide staining, styox green assay and DNA interaction study, therefore both compounds were tested for molecular docking studies against tyrosine kinase to support cytotoxic activity.

Conclusion: This study revealed that the plant extracts and isolated compounds possess promising antiproliferative activity against HepG-2 cell lines via apoptotic cell death.

Keywords: Anchusa arvensis, Cytotoxicity, 3-(4, 5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide, Anticancer activity, HepG-2 cell lines, Para–methoxycatechol, Decane.

« Previous
Graphical Abstract

[1]
Tiwary, B.K.; Bihani, S.; Kumar, A.; Chakraborty, R.; Ghosh, R. The in vitro cytotoxic activity of ethno-pharmacological important plants of Darjeeling district of West Bengal against different human cancer cell lines. BMC Complement. Altern. Med., 2015, 15(1), 22.
[http://dx.doi.org/10.1186/s12906-015-0543-5] [PMID: 25887417]
[2]
Gali, K.; Ramakrishnan, G.; Kothai, R.; Jaykar, B. In-vitro anti-cancer activity of methanolic extract of leaves of Argemone mexicana Linn. Int. J. Pharm. Tech. Res., 2011, 3, 1329-1333.
[3]
Tang, Z-Y.; Ye, S-L.; Liu, Y-K.; Qin, L-X.; Sun, H-C.; Ye, Q-H.; Wang, L.; Zhou, J.; Qiu, S-J.; Li, Y.; Ji, X.N.; Liu, H.; Xia, J.L.; Wu, Z.Q.; Fan, J.; Ma, Z.C.; Zhou, X.D.; Lin, Z.Y.; Liu, K.D. A decade’s studies on metastasis of hepatocellular carcinoma. J. Cancer Res. Clin. Oncol., 2004, 130(4), 187-196.
[http://dx.doi.org/10.1007/s00432-003-0511-1] [PMID: 14685850]
[4]
Cragg, G.M.; Newman, D.J. Plants as a source of anti-cancer agents. J. Ethnopharmacol., 2005, 100(1-2), 72-79.
[http://dx.doi.org/10.1016/j.jep.2005.05.011] [PMID: 16009521]
[5]
Newman, D.J.; Cragg, G.M.; Snader, K.M. Natural products as sources of new drugs over the period 1981-2002. J. Nat. Prod., 2003, 66(7), 1022-1037.
[http://dx.doi.org/10.1021/np030096l] [PMID: 12880330]
[6]
Moudi, M.; Go, R.; Yien, C.Y.S.; Nazre, M. Vinca alkaloids. Int. J. Prev. Med., 2013, 4(11), 1231-1235.
[PMID: 24404355]
[7]
Basili, S.; Moro, S. Novel camptothecin derivatives as topoisomerase I inhibitors. Expert Opin. Ther. Pat., 2009, 19(5), 555-574.
[http://dx.doi.org/10.1517/13543770902773437] [PMID: 19441934]
[8]
Dafni, A.; Yaniv, Z.; Palevitch, D. Ethnobotanical survey of medicinal plants in northern Israel. J. Ethnopharmacol., 1984, 10(3), 295-310.
[http://dx.doi.org/10.1016/0378-8741(84)90017-5] [PMID: 6748708]
[9]
Ali-Shtayeh, M.S.; Yaniv, Z.; Mahajna, J. Ethnobotanical survey in the Palestinian area: a classification of the healing potential of medicinal plants. J. Ethnopharmacol., 2000, 73(1-2), 221-232.
[http://dx.doi.org/10.1016/S0378-8741(00)00316-0] [PMID: 11025160]
[10]
El Beyrouthy, M.; Arnold, N.; Delelis-Dusollier, A.; Dupont, F. Plants used as remedies antirheumatic and antineuralgic in the traditional medicine of Lebanon. J. Ethnopharmacol., 2008, 120(3), 315-334.
[http://dx.doi.org/10.1016/j.jep.2008.08.024] [PMID: 18809483]
[11]
Al-Snafi, A. The pharmacology of Anchusa italica and Anchusa strigosa–A review. Int. J. Pharm. Pharm. Sci., 2014, 6(4), 7-10.
[12]
Sharifi-Rad, J.; Miri, A.; Alfatemi, S.M.H.; Rad, M.S. A study of Antibacterial potentiality of some plants extracts against multi-drug resistant human pathogens. Ann. Biol. Res., 2013, 8(4), 35-41.
[13]
Tsermentseli, S.; Assimopoulou, A.; Gianovits-Argyriadou, N.; Kanaze, F.; Papageorgiou, V. Phytochemical analysis of Anchusa arvensis roots. Planta Med., 2008, 74(09), PC53.
[http://dx.doi.org/10.1055/s-0028-1084571]
[14]
Khan, H.; Saeed, M.; Gilani, A.H.; Muhammad, N.; Haq, I.U.; Ashraf, N.; Rehman, N.U.; Haleemi, A. Antipyretic and anticonvulsant activity of Polygonatum verticillatum: comparison of rhizomes and aerial parts. Phytother. Res., 2013, 27(3), 468-471.
[http://dx.doi.org/10.1002/ptr.4721] [PMID: 22610947]
[15]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[16]
Oommen, S.; Anto, R.J.; Srinivas, G.; Karunagaran, D. Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. Eur. J. Pharmacol., 2004, 485(1-3), 97-103.
[http://dx.doi.org/10.1016/j.ejphar.2003.11.059] [PMID: 14757128]
[17]
Gerlach, S.L.; Rathinakumar, R.; Chakravarty, G.; Göransson, U.; Wimley, W.C.; Darwin, S.P.; Mondal, D. Anticancer and chemosensitizing abilities of cycloviolacin 02 from Viola odorata and psyle cyclotides from Psychotria leptothyrsa. Biopolymers, 2010, 94(5), 617-625.
[http://dx.doi.org/10.1002/bip.21435] [PMID: 20564026]
[18]
Sirajuddin, M.; Ali, S.; Badshah, A. Drug-DNA interactions and their study by UV-Visible, fluorescence spectroscopies and cyclic voltametry. J. Photochem. Photobiol. B, 2013, 124, 1-19.
[http://dx.doi.org/10.1016/j.jphotobiol.2013.03.013] [PMID: 23648795]
[19]
Mphahlele, M.J.; Paumo, H.K.; Choong, Y.S. Synthesis and In Vitro Cytotoxicity of the 4-(Halogenoanilino)-6-bromoquinazolines and Their 6-(4-Fluorophenyl) Substituted Derivatives as Potential Inhibitors of Epidermal Growth Factor Receptor Tyrosine Kinase. Pharmaceuticals (Basel), 2017, 10(4), 87.
[http://dx.doi.org/10.3390/ph10040087] [PMID: 29156606]
[20]
Xu, M.; Zhang, M.; Wang, D.; Yang, C.R.; Zhang, Y.J. Phenolic compounds from the whole plants of Gentiana rhodantha (Gentianaceae). Chem. Biodivers., 2011, 8(10), 1891-1900.
[http://dx.doi.org/10.1002/cbdv.201000220] [PMID: 22006717]
[21]
Bahmanzadegan, A.; Rowshan, V.; Zareiyan, F.; Hatami, A. Essential oil composition, free radical scavenging activity and polyphenolic content of Gaillonia eriantha Jaub. & Spach from Iran. Nat. Prod. Res., 2017, 31(11), 1343-1346.
[http://dx.doi.org/10.1080/14786419.2016.1244199] [PMID: 27806651]
[22]
Jakštys, B.; Ruzgys, P.; Tamošiūnas, M.; Šatkauskas, S. Different cell viability assays reveal inconsistent results after bleomycin electrotransfer in vitro. J. Membr. Biol., 2015, 248(5), 857-863.
[http://dx.doi.org/10.1007/s00232-015-9813-x] [PMID: 26077843]
[23]
Zhang, L.; Zeng, D.; Chen, Y.; Li, N.; Lv, Y.; Li, Y.; Xu, X.; Xu, G. miR-937 contributes to the lung cancer cell proliferation by targeting INPP4B. Life Sci., 2016, 155, 110-115.
[http://dx.doi.org/10.1016/j.lfs.2016.05.014] [PMID: 27179609]
[24]
Upur, H.; Yusup, A.; Baudrimont, I.; Umar, A.; Berke, B.; Yimit, D.; Lapham, J. C.; Creppy, E. E.; Moore, N. Inhibition of cell growth and cellular protein, DNA and RNA synthesis in human hepatoma (HepG2) cells by ethanol extract of abnormal Savda Munziq of traditional Uighur medicine. Evid Based Complement Alternat Med, 2011, 2011
[http://dx.doi.org/10.1093/ecam/nen062]
[25]
Nair, P.K.R.; Melnick, S.J.; Wnuk, S.F.; Rapp, M.; Escalon, E.; Ramachandran, C. Isolation and characterization of an anticancer catechol compound from Semecarpus anacardium. J. Ethnopharmacol., 2009, 122(3), 450-456.
[http://dx.doi.org/10.1016/j.jep.2009.02.001] [PMID: 19429311]
[26]
Yang, S.; Zhao, Q.; Xiang, H.; Liu, M.; Zhang, Q.; Xue, W.; Song, B.; Yang, S. Antiproliferative activity and apoptosis-inducing mechanism of constituents from Toona sinensis on human cancer cells. Cancer Cell Int., 2013, 13(1), 12.
[http://dx.doi.org/10.1186/1475-2867-13-12] [PMID: 23394678]
[27]
Collins, J.A.; Schandi, C.A.; Young, K.K.; Vesely, J.; Willingham, M.C. Major DNA fragmentation is a late event in apoptosis. J. Histochem. Cytochem., 1997, 45(7), 923-934.
[http://dx.doi.org/10.1177/002215549704500702] [PMID: 9212818]
[28]
Liu, M.; Yang, S.; Jin, L.; Hu, D.; Wu, Z.; Yang, S. Chemical constituents of the ethyl acetate extract of Belamcanda chinensis (L.) DC roots and their antitumor activities. Molecules, 2012, 17(5), 6156-6169.
[http://dx.doi.org/10.3390/molecules17056156] [PMID: 22627971]
[29]
Elumalai, P.; Gunadharini, D.N.; Senthilkumar, K.; Banudevi, S.; Arunkumar, R.; Benson, C.S.; Sharmila, G.; Arunakaran, J. Induction of apoptosis in human breast cancer cells by nimbolide through extrinsic and intrinsic pathway. Toxicol. Lett., 2012, 215(2), 131-142.
[http://dx.doi.org/10.1016/j.toxlet.2012.10.008] [PMID: 23089555]
[30]
Cox, P.J.; Psomas, G.; Bolos, C.A. Characterization and DNA-interaction studies of 1,1-dicyano-2,2-ethylene dithiolate Ni(II) mixed-ligand complexes with 2-amino-5-methyl thiazole, 2-amino-2-thiazoline and imidazole. Crystal structure of [Ni(i-MNT)(2a-5mt)(2)]. Bioorg. Med. Chem., 2009, 17(16), 6054-6062.
[http://dx.doi.org/10.1016/j.bmc.2009.06.058] [PMID: 19608424]
[31]
Shahabadi, N.; Mohammadi, S.; Alizadeh, R. DNA interaction studies of a new platinum (II) complex containing different aromatic dinitrogen ligands. Bioinorg. Chem. Appl., 2011, 2011 429241
[http://dx.doi.org/10.1155/2011/429241]

Rights & Permissions Print Cite
Article Metrics
18
© 2024 Bentham Science Publishers | Privacy Policy