Login Register Cart 0
Generic placeholder image

The Natural Products Journal

Editor-in-Chief

ISSN (Print): 2210-3155
ISSN (Online): 2210-3163

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

Cytotoxic and Apoptotic Action of Nonactin and Cephaeline. HBr Precludes Alteration of Redox Status

Author(s): Oluyomi Stephen Adeyemi*, Oluwakemi Josephine Awakan, Anne Adebukola Adeyanju and David Adeiza Otohinoyi

Volume 9, Issue 4, 2019

Page: [295 - 302] Pages: 8

DOI: 10.2174/2210315508666181010143636

Price: $65

Abstract

Background: Natural products or naturally derived compounds are invaluable to human and animal lives either for nutritional value or for medicinal purposes. Indeed, natural products including extracts containing polychemical mixtures play a leading role in the discovery and development of drugs. However, the increasing interest in natural medicines is also attracting a growing concern about the safety of naturally derived medications.

Objective: In the present study, we evaluated several naturally derived compounds for in vitro cytotoxicity in mammalian cells.

Methods: A total of 54 compounds were evaluated for in vitro cytotoxic and apoptotic action in Human Fibroblast Foreskin (HFF) cells.

Results: Of the 54 natural compounds screened for cellular toxicity, only nonactin and cephaeline. HBr reduced cellular viability by ≥60% with IC50 value <3 µg/ml. Addition of trolox antioxidant to the assay medium failed to abate cellular toxicity by both nonactin and cephaeline.HBr treatments. Fluorescence evaluation for Reactive Oxygen Species (ROS) production as well as Mitochondrial Membrane Potential (MMP) was negative for both nonactin and cephaeline.HBr treatments. In contrast, both nonactin and cephaeline.HBr caused cellular apoptosis and this was not attenuated even in the presence of trolox.

Conclusion: Taken together, we show evidence supporting that cytotoxic and apoptotic action of nonactin and cephaeline.HBr precludes oxidative stress or ROS production.

Keywords: Cellular death, natural products, oxidative stress, toxicity, cytotoxic, nonactin.

Graphical Abstract

[1]
Seelinger, M.; Popescu, R.; Giessrigl, B.; Jarukamjorn, K.; Unger, C.; Wallnöfer, B.; Fritzer-Szekeres, M.; Szekeres, T.; Diaz, R.; Jäger, W.; Frisch, R.; Kopp, B.; Krupitza, G. Methanol extract of the ethnopharmaceutical remedy Smilax spinosa exhibits anti-neoplastic activity. Int. J. Oncol., 2012, 41(3), 1164-1172.
[http://dx.doi.org/10.3892/ijo.2012.1538] [PMID: 22752086]
[2]
Fadeyi, S.A.; Fadeyi, O.O.; Adejumo, A.A.; Okoro, C.; Myles, E.L. In vitro anticancer screening of 24 locally used Nigerian medicinal plants. BMC Complement. Altern. Med., 2013, 13, 79.
[http://dx.doi.org/10.1186/1472-6882-13-79] [PMID: 23565862]
[3]
Farnsworth, N.R. Screening plants for new medicines; National Academy Press: Washington, D.C, 1988.
[4]
Kim, J.; Park, E.J. Cytotoxic anticancer candidates from natural resources. Curr. Med. Chem. Anticancer Agents, 2002, 2(4), 485-537.
[http://dx.doi.org/10.2174/1568011023353949] [PMID: 12678733]
[5]
Mann, J. Natural products in cancer chemotherapy: Past, present and future. Nat. Rev. Cancer, 2002, 2(2), 143-148.
[http://dx.doi.org/10.1038/nrc723] [PMID: 12635177]
[6]
Grabley, S.; Thiericke, R. Bioactive agents from natural sources: Trends in discovery and application. Adv. Biochem. Eng. Biotechnol., 1999, 64, 101-154.
[http://dx.doi.org/10.1007/3-540-49811-7_4] [PMID: 9933977]
[7]
Cragg, G.M.; Grothaus, P.G.; Newman, D.J. Impact of natural products on developing new anti-cancer agents. Chem. Rev., 2009, 109(7), 3012-3043.
[http://dx.doi.org/10.1021/cr900019j] [PMID: 19422222]
[8]
Gordaliza, M. Natural products as leads to anticancer drugs. Clin. Transl. Oncol., 2007, 9(12), 767-776.
[http://dx.doi.org/10.1007/s12094-007-0138-9] [PMID: 18158980]
[9]
Zhang, Z.; Du, G.J.; Wang, C.Z.; Wen, X.D.; Calway, T.; Li, Z.; He, T.C.; Du, W.; Bissonnette, M.; Musch, M.W.; Chang, E.B.; Yuan, C.S. Yuan, C.S. Compound K, a ginsenoside metabolite, inhibits colon cancer growth via multiple pathways including p53-p21 interactions. Int. J. Mol. Sci., 2013, 14(2), 2980-2995.
[http://dx.doi.org/10.3390/ijms14022980] [PMID: 23434653]
[10]
Zhang, A.; Sun, H.; Yan, G.; Wang, P.; Han, Y.; Wang, X. Metabolomics in diagnosis and biomarker discovery of colorectal cancer. Cancer Lett., 2014, 345(1), 17-20.
[http://dx.doi.org/10.1016/j.canlet.2013.11.011] [PMID: 24333717]
[11]
Keller-Schierlein, W.; Gerlach, H. Macrotetrolides. Fortschr. Chem. Org. Naturst., 1968, 26, 161-189.
[http://dx.doi.org/10.1007/978-3-7091-7134-9_4] [PMID: 4881902]
[12]
Corbaz, R.; Ettlinger, L.; Gäumann, E.; Keller-Schierlein, W.; Kradolfer, F.; Neipp, L.; Prelog, V.; Zähner, H. Stoffwechselprodukte von Actinomyceten. 3. Mitteilung. Nonactin. Helv. Chim. Acta, 1955, 38(6), 1445-1448.
[http://dx.doi.org/10.1002/hlca.19550380617]
[13]
Fleming, I.; Ghosh, S.K. A total synthesis of nonactin. J. Chem. Soc. Chem. Commun., 1994, 19, 2287-2289.
[http://dx.doi.org/10.1039/c39940002287]
[14]
Meyers, E.; Pansy, F.E.; Perlman, D.; Smith, D.A.; Weisenborn, F.L.J. The in vitro activity of nonactin and its homologs: monactin, dinactin and trinactin. J. Antibiot., 1965, 18, 128-129.
[PMID: 14336167]
[15]
Borrel, M.N.; Pereira, E.; Fiallo, M.; Garnier-Suillerot, A. Analysis of multidrug transporter in living cells inhibition of p-glycoprotein-mediated efflux of anthracyclines by ionophores. Met. Based Drugs, 1994, 1(2-3), 175-182.
[http://dx.doi.org/10.1155/MBD.1994.175] [PMID: 18476229]
[16]
Lipinski, C.A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods, 2000, 44(1), 235-249.
[http://dx.doi.org/10.1016/S1056-8719(00)00107-6] [PMID: 11274893]
[17]
Lara, A.; Valverde, R.; Gomez, L.; Hidalgo, N. Micropropagacion de la planta medicinal psychotria acuminate. Agron. Costarric., 2003, 27(2), 7-20.
[18]
Maxwell, G.M. The Alimentary System. Principles of Paediatric Pharmacology; Springer: Boston, 1984, pp. 204-216.
[http://dx.doi.org/10.1007/978-1-4684-7544-9_9]
[19]
Adeyemi, O.S.; Murata, Y.; Sugi, T.; Kato, K. Inorganic nanoparticles caused death of Toxoplasma gondii through alteration of redox status and mitochondrial membrane potential. Int. J. Nanomedicine, 2017, 12, 1647-1661.
[http://dx.doi.org/10.2147/IJN.S122178] [PMID: 28280332]
[20]
Ogbonnia, S.O.; Nkemehule, F.E.; Anyika, E.N. Evaluation of acute and subchronic toxicity of Stachytarpheta angustifolia (Mill) Vahl (Fam. Verbanaceae) extract in animals. J. Biotechnol., 2009, 8(9), 1793-1799.
[21]
Ogbonnia, S.O.; Mbaka, G.O.; Igbokwe, N.H.; Anyika, E.N.; Alli, P.; Nwakakwa, N. Antimicrobial evaluation, acute and subchronic toxicity studies of Leone Bitters, a Nigerian polyherbal formulation, in rodents. Agric. Biol. J. N. Am., 2010, 1(3), 366-376.
[http://dx.doi.org/10.5251/abjna.2010.1.3.366.376]
[22]
Ovadje, P.; Roma, A.; Steckle, M.; Nicoletti, L.; Arnason, J.T.; Pandey, S. Advances in the research and development of natural health products as main stream cancer therapeutics. Evid. Based Complement. Alternat. Med., 2015, 2015 Article ID 751348
[http://dx.doi.org/10.1155/2015/751348] [PMID: 25883673]
[23]
Adeyemi, O.S.; Sykes, M.L.; Akanji, M.A.; Avery, V.M. Anti-trypanosoma and cytotoxic activity of ethanolic extracts of Psidium guajava leaves in Alamar Blue based assays. Vet. Arh., 2011, 81(5), 623-633.
[24]
Adeyemi, O.S.; Sugi, T.; Han, Y.; Kato, K. Screening of chemical compound libraries identified new anti-Toxoplasma gondii agents. Parasitol. Res., 2018, 117(2), 355-363.
[http://dx.doi.org/10.1007/s00436-017-5698-1] [PMID: 29260298]
[25]
General guidelines for methodologies in research and evaluation of 100 traditional medicine, 2000. Available from: https://apps.who. int/iris/handle/10665/66783
[26]
Joshua, A.J.; Goudar, K.S.; Sameera, N.; Kumar, P.G.; Murali, B.; Dinakar, B.; Amit, A. Safety assessment of herbal formulations, Rumbion™ and Tyrel™ in albino wistar rats. Am. J. Pharmacol. Toxicol., 2010, 5(1), 42-47.
[http://dx.doi.org/10.3844/ajptsp.2010.42.47]
[27]
Adisa, R.; Fakeye, T. Assessment of the knowledge of community pharmacists regarding common phytopharmaceuticals sold in south western nigeria. Trop. J. Pharm. Res., 2006, 5(2), 619-625.
[28]
Osorio, E.J.; Robledo, S.M.; Bastida, J. The alkaloids with antiprotozoal activity., 2008, 66, 113-190.
[29]
Harinantenaina Rakotondraibe, L.; Rasolomampianina, R.; Park, H.Y.; Li, J.; Slebodnik, C.; Brodie, P.J.; Blasiak, L.C.; Hill, R.; TenDyke, K.; Shen, Y.; Cassera, M.B.; Rejo, F.; Kingston, D.G. Antiproliferative and antiplasmodial compounds from selected Streptomyces species. Bioorg. Med. Chem. Lett., 2015, 25(23), 5646-5649.
[http://dx.doi.org/10.1016/j.bmcl.2015.07.103] [PMID: 26508548]
[30]
Deepa, P.R.; Vandhana, S.; Jayanthi, U.; Krishnakumar, S. Therapeutic and toxicologic evaluation of anti-lipogenic agents in cancer cells compared with non-neoplastic cells. Basic Clin. Pharmacol. Toxicol., 2012, 110(6), 494-503.
[http://dx.doi.org/10.1111/j.1742-7843.2011.00844.x] [PMID: 22151915]
[31]
Cha, M.C.; Lin, A.; Meckling, K.A. Low dose docosahexaenoic acid protects normal colonic epithelial cells from araC toxicity. BMC Pharmacol., 2005, 5, 7.
[http://dx.doi.org/10.1186/1471-2210-5-7] [PMID: 15788091]
[32]
Zhang, W.; Robert, A.; Vogensen, S.B.; Howe, J.R. The relationship between agonist potency and AMPA receptor kinetics. Biophys. J., 2006, 91(4), 1336-1346.
[http://dx.doi.org/10.1529/biophysj.106.084426] [PMID: 16731549]
[33]
Mukhopadhyay, R.; Kazi, J.; Debnath, M.C. Synthesis and characterization of copper nanoparticles stabilized with Quisqualis indica extract: Evaluation of its cytotoxicity and apoptosis in B16F10 melanoma cells. Biomed. Pharmacother., 2018, 97, 1373-1385.
[http://dx.doi.org/10.1016/j.biopha.2017.10.167] [PMID: 29156527]
[34]
Ju, Y.L.; Byeang, H.K. Total synthesis of nonactin. Tetrahedron, 1996, 52(2), 571.
[http://dx.doi.org/10.1016/0040-4020(95)00913-2]

Rights & Permissions Print Cite
Article Metrics
41
2
1
1
© 2024 Bentham Science Publishers | Privacy Policy