Cytotoxicity and cytochrome P450 inhibitory activities of Clinacanthus nutans
-
Suk Yen Quah
,
Gabriel Akyirem Akowuah
Abstract
Background:
Clinacanthus nutans Lindau (family: Acanthaceae), also known as “Sabah Snake Grass” or “Belalai Gajah” in Malaysia, has been widely used by Malaysians due to its anticancer property. However, the anticancer activity of C. nutans leaves extract and its safe use need to be further investigated. The objectives of the present study were to evaluate the cytotoxic effects of methanol leaves extract of C. nutans in various human cancer cell lines and to evaluate the in vitro effect of C. nutans leaves on the activity of CYP3A4 and CYP2E1 in human liver microsomes.
Methods:
The cytotoxic effects of methanol extract of C. nutans leaves in various cancer cell lines (Hep-G2, A549, HT-29, MDA-MB-231, MCF-7, and CRL 1739) and normal cells (3T3) were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The activities of CYP3A4 and CYP2E1 were determined using simple spectrophotometric methods.
Results:
Results obtained showed that the methanol extract of C. nutans leaves exhibited the highest cytotoxic effect against Hep-G2 cell lines (liver cancer) (IC50=13.33 μg/mL), followed by breast cancer oestrogen negative (MDA-MB-231) (IC50 of 18.67 μg/mL). Methanol leaves extract of C. nutans showed significant inhibition (p<0.05) in CYP3A4 and CYP2E1 activity in human liver microsomes.
Conclusions:
In conclusion, methanol leaves extract of C. nutans exhibited the highest cytotoxic activity against liver cancer cells (Hep-G2). There is a possibility that herb-drug interaction could occur with C. nutans through inhibitory effects on CYP3A4. Additionally, inhibition of C. nutans on CYP2E1 could show anti-carcinogenesis effects in human liver microsomes.
Acknowledgments
The authors are grateful for the technical supports from the Faculty of Pharmaceutical Sciences and financial supports from CERVIE, UCSI, University research funding (Proj-In-FPS-003 and Proj-In-FPS-004) to carry out the work successfully.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Health Facts 2014: Ministry of Health Malaysia. Available at: http://www.moh.gov.my/images/gallery/publications/HEALTH%20FACTS%202014.pdf. Accessed: 19 June 2016.Search in Google Scholar
2. Roosita K, Kusharto CM, Sekiyama M, Fachrurozi Y, Ohtsuka R. Medicinal plants used by the villagers of a Sundanese Community in West Java, Indonesia. J Ethnopharmacol 2008;115:72–81.10.1016/j.jep.2007.09.010Search in Google Scholar
3. Dhanoa A, Yong TL, Yeap SJ, Lee IS, Singh VA. Complementary and alternative medicine useamongst Malaysian orthopaedic oncology patients. BMC Complement Altern Med 2014;14:404.10.1186/1472-6882-14-404Search in Google Scholar
4. Sakdarat S, Shuyprom A, Dechatiwongse N, Ayudhya T, Waterman PG, Karagianis G. Chemical composition investigation of Clinacanthus nutans Lindau leaves. Thai J Phytopharmacol 2006;13:13–24.Search in Google Scholar
5. John M. Herbal remedies: adverse effects and drug interactions. Am Fam Physicians 1999;59:1239–44.Search in Google Scholar
6. Tsai H-H, Lin H-W, Pickard SA, Mahady GB. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract 2012;66:1019–20.10.1111/j.1742-1241.2012.03008.xSearch in Google Scholar
7. McCarty MC. Inhibition of CYP2E1 with natural agents may be a feasible strategy for minimizing the hepatotoxicity of ethanol. Med Hypotheses 2001;56:8–11.10.1054/mehy.1999.1015Search in Google Scholar
8. P’ng XW, Akowuah GA, Chin JH. Evaluation of the sub-acute oral toxicity effect of methanol extract of Clinacanthus nutans in rats. J Acute Dis 2013;2:29–32.10.1016/S2221-6189(13)60090-6Search in Google Scholar
9. Lee B, Huang Y, Wu S. Hepatoprotective activity of fresh Polygonum multiflorum against HEP G2 hepatocarcinoma cell proliferation. J Food Drug Anal 2011;19:26–32.10.38212/2224-6614.2172Search in Google Scholar
10. Nash T. The colorimetric estimation of formation of formaldehyde means of Hantzsch reactions. J Biol Chem 1953;55:416–22.10.1042/bj0550416Search in Google Scholar
11. Gibson G, Skett P. Introduction to drug metabolism, 2nd ed. UK: Blackie Academic & Professional, 1994.10.1007/978-1-4899-6844-9Search in Google Scholar
12. Cederbaum AI. Methodology to assay CYP2E1 mixed function oxidase catalytic activity and its induction. Redox Biol 2014;2C:1048–54.10.1016/j.redox.2014.09.007Search in Google Scholar PubMed PubMed Central
13. Mustapa AN, Martin A, Mato RB, Cocero MJ. Extarction of phytocompounds from the medicinal plant Clinacanthus nutans by microwave-assisted extraction and supercritical carbon dioxide extraction. Ind Crop Prod 2015;74:83–94.10.1016/j.indcrop.2015.04.035Search in Google Scholar
14. Huang D. Clinacanthus nutans ethanol extract inhibits a hepatoma in mice through upregulation of the immune response. Molecules 2015;20:17405–28.10.3390/molecules200917405Search in Google Scholar PubMed PubMed Central
15. Khoo LW, Mediani A, Zolkeflee NK, Leong SW, Ismail IS, Khatib A, et al. Phytochemical diversity of Clinacanthus nutans extracts and their bioactivity correlations elucidated by NMR based metabolomics. Phytochem Lett 2015;14:123–3.10.1016/j.phytol.2015.09.015Search in Google Scholar
16. Stefek M. Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract. Interdiscipl Toxicol 2011;4:69–77.10.2478/v10102-011-0013-ySearch in Google Scholar PubMed PubMed Central
17. Boik J. Natural compounds in cancer therapy. Princeton: Oregon Medical Press, 2001.Search in Google Scholar
18. Teshima K, Kaneko T, Ohtani K, Kasai R, Lhieochaiphant S, Picheansoonthon C. C-glycosyl flavones from Clinacanthus nutans. Nat Med 1997;51:557.Search in Google Scholar
19. Tiew WP, P’ng XW, Chin JH, Gabriel AA. Effect of methanol extract of Clinacanthus nutans on serum biochemical parameters in rats. J Appl Pharm 2014;6:77–86.10.21065/19204159.6.77Search in Google Scholar
20. Zheng XX, Zhang RS, Zhou YJ, Wang JG. Role of ERK/FoxO3a signal axis in inhibitory effect of vitexin 1 (VB-1) in HepG2 cell proliferation. China J Chin Mater Med 2014;39:1276–9.Search in Google Scholar
21. Yuan L, Wang J, Xiao H, Xiao C, Wang Y. Isoorientin induces apoptosis through mitochondrial dysfunction and inhibition of PI3K/Akt signaling pathway in HepG2 cancer cells. Toxicol Appl Pharm 2012;265:83–92.10.1016/j.taap.2012.09.022Search in Google Scholar PubMed
22. Sweeney BP, Bromilow J. Liver enzyme induction and inhibition: implications for anesthesia. J Anesth 2006;61:159–77.10.1111/j.1365-2044.2005.04462.xSearch in Google Scholar PubMed
23. Gonzalez FJ. The 2006 Bernard B. Brodie award lecture. Cyp2e1. Drug Metab Dispos 2007;35:1–8.10.1124/dmd.106.012492Search in Google Scholar PubMed
24. Durovcova E, Rabajdova MR, Birkova A, Urban P, Gregova K. Naturally occurring substances and their role in chemo-protective effects. Cent Eur J Public Health 2013;21:213–9.10.21101/cejph.a3886Search in Google Scholar PubMed
25. Ye Q, Lian F, Chavez PR, Chung J, Ling W, Qin H, et al. Cytochrome P450 2E1 inhibition prevents hepatic carcinogenesis induced by diethylnitrosamine in alcohol-fed rats. Hepatobiliary Surg Nutr 2012;1:5–18.Search in Google Scholar
26. Yang CS, Chhabra S, Hong J, Smith TJ. Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sulfide (DAS) and related compounds from garlic. J Nutr 2001;131:10415–55.10.1093/jn/131.3.1041SSearch in Google Scholar PubMed
27. Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol 2013;4:1–10.10.3389/fphar.2013.00177Search in Google Scholar PubMed PubMed Central
28. Clifford MN, Brown JE. Dietary flavonoids and health-broadening the perspective. In: Anderson OM, Markham KR, editors. Flavonoids: chemistry, biochemistry and applications. US: CRC Press Taylor & Francis Group 2006:319–30.10.1201/9781420039443.ch6Search in Google Scholar
29. Chao P, Hsiu S, Hou Y. Flavonoids in herbs: biological fates and potential interactions with xenobiotics. J Food Drug Anal 2002;10:219–28.Search in Google Scholar
30. Shimada T, Tanaka K, Takenaka S, Murayama N, Martin MV, Foroozesh MK, et al. Structure-function relationships of inhibition of human cytochromes P450 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 flavonoid derivatives. Chem Res Toxicol 2010;23:1921–35.10.1021/tx100286dSearch in Google Scholar PubMed PubMed Central
©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Review of pharmacogenetics studies of L-asparaginase hypersensitivity in acute lymphoblastic leukemia points to variants in the GRIA1 gene
- Population Pharmacogenomics
- Genetic polymorphisms of cytochrome P450 enzymes: CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in the Croatian population
- Original Articles
- Role of treatment-modifying MTHFR677C>T and 1298A>C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy
- Genotyping CYP2D6 by three different methods: advantages and disadvantages
- Relationship between metabolic phenotypes and genotypes of CYP1A2 and CYP2A6 in the Nigerian population
- Influence of genetic polymorphisms of CYP3A5 and ABCB1 on sirolimus pharmacokinetics, patient and graft survival and other clinical outcomes in renal transplant
- Cytotoxicity and cytochrome P450 inhibitory activities of Clinacanthus nutans
- Verification of propofol sulfate as a further human propofol metabolite using LC-ESI-QQQ-MS and LC-ESI-QTOF-MS analysis
Articles in the same Issue
- Frontmatter
- Review
- Review of pharmacogenetics studies of L-asparaginase hypersensitivity in acute lymphoblastic leukemia points to variants in the GRIA1 gene
- Population Pharmacogenomics
- Genetic polymorphisms of cytochrome P450 enzymes: CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in the Croatian population
- Original Articles
- Role of treatment-modifying MTHFR677C>T and 1298A>C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy
- Genotyping CYP2D6 by three different methods: advantages and disadvantages
- Relationship between metabolic phenotypes and genotypes of CYP1A2 and CYP2A6 in the Nigerian population
- Influence of genetic polymorphisms of CYP3A5 and ABCB1 on sirolimus pharmacokinetics, patient and graft survival and other clinical outcomes in renal transplant
- Cytotoxicity and cytochrome P450 inhibitory activities of Clinacanthus nutans
- Verification of propofol sulfate as a further human propofol metabolite using LC-ESI-QQQ-MS and LC-ESI-QTOF-MS analysis
