Evaluation of the Anticancer Effect of Xanthium Strumarium Root Extract on Human Epithelial Ovarian Cancer Cells Using 1H NMR-Based Metabolomics

Document Type : Original Research Articles

Authors
Roya Malekzadeh 1
Mohammad Arjmand 2
Reza Haji Hosseini 3
Atusa Vaziri 3
Zahra Zamani 4
1 Metabolomics Lab. Biochemistry Dept. Pasteur INstitute of Iran, Dept. Of Biology, Payame Noor University, Tehran, Iran
2 Metabolomics Lab. Biochemistry Dpt. Pasteur Institute of Iran
3 Dept. of Biology, Payame Noor University, Tehran, Iran
4 Metabolomics Lab. Biochemistry Dept. Pasteur Institute of Iran, Tehran, Iran
10.22059/jsciences.2020.291407.1007458
Abstract
Epithelial Ovarian cancer is the leading cause of cancer mortality among women all over the world. As chemotherapeutics has many side effects, researchers have focused on the potential use of medicinal plants as natural antitumor agents. Xanthium strumarium studied in this work as an herbal anticancer agent. This study aimed to evaluate the antitumor effect and metabolic alterations caused by the root extract of X. strumarium on human ovarian cancer cell line (A2780cp), using NMR-based metabolomics approaches. Cells were cultured and treated with different concentrations of the ethanolic plant extract. Antitumor activity determined by MTT assay and cell metabolites extracted for NMR spectroscopy. 1H NMR spectroscopy was applied, and outliers were analyzed using multivariate statistical analysis techniques. The extract exhibited antitumor activity against ovarian cancer cells with an IC50 of 6 μg/ml after 48 hours of treatment. The most affected metabolic pathways in the experimental groups were limited to tyrosine metabolism, nucleotide metabolism, fatty acid biosynthesis, and glycerolipid metabolism. Our data showed that the ethanolic root extract of X. strumarium has antitumor activity on the ovarian cancer cells and can affect vital metabolic pathways. However, further studies required to validate this activity.
Keywords
Xanthium strumarium
Epithelial ovarian cancer
A2780cp cell line
Metabolomics
1H NMR
  1. Vaishnav K., George L.B. & Highland H. N. Antitumour activity of Xanthium strumarium L. on human cervical cancer HeLa cells. J. Cancer Tumor Int. 1–13 (2015).
  2. Siegel R. L., Miller K. D. & Jemal A. Cancer statistics, 2016. CA. Cancer J. Clin. 66: 7–30 (2016).
  3. Smith R. A., Andrews KS., Brooks D., Fedewa SA., Manassaram-Baptiste D., Saslow D., Wender RC. Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening. CA. Cancer J. Clin. 69: 184–210 (2019).
  4. Zhong L. X., Wu M.L., Li H., Liu J. & Lin L.Z. Efficacy and safety of intraperitoneally administered resveratrol against rat orthotopic ovarian cancers. Cancer Manag. Res. 11: 6113 (2019).
  5. Lichota A. & Gwozdzinski K. Anticancer activity of natural compounds from plant and marine environment. Int. J. Mol. Sci. 19: 3533 (2018).
  6. Al-Mekhlafi F. A., Abutaha N., Mashaly AMA., Nasr FA., Ibrahim KE., Wadaan MA. Biological activity of Xanthium strumarium seed extracts on different cancer cell lines and Aedes caspius, Culex pipiens (Diptera: Culicidae). Saudi J. Biol. Sci. 24: 817–821 (2017).
  7. Fan W., Fan L., Peng C., Zhang Q., Wang L., Li L., Wang J., Zhang D., Peng W., Wu C. Traditional Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Xanthium strumarium L.: A Review. Molecules 24: 359 (2019).
  8. Klenkar J. & Molnar M. Natural and synthetic coumarins as potential anticancer agents. J. Chem. Pharm. Res 7: 1223–1238 (2015).
  9. Pinu F. R., Goldansaz S. A. & Jaine J. Translational Metabolomics: Current Challenges and Future Opportunities. Metabolites 9.108 (2019).
  10. Emwas A.-H., Roy R., McKay RT., Tenori L., Saccenti E., Gowda GAN., Raftery D., Alahmari F., Jaremko L., Jaremko M., Wishart DS. NMR spectroscopy for metabolomics research. Metabolites 9: 123 (2019).
  11. Scherer R. & Godoy H. T. Effects of extraction methods of phenolic compounds from Xanthium strumarium L. and their antioxidant activity. Rev. Bras. Plantas Med. 16: 41–46 (2014).
  12. Gottschalk M., Ivanova G., Collins DM., Eustace A., OConnor R., Brougham DF. Metabolomic studies of human lung carcinoma cell lines using in vitro 1H NMR of whole cells and cellular extracts. NMR Biomed. An Int. J. Devoted to Dev. Appl. Magn. Reson. vivo 21: 809–819 (2008).
  13. Sheedy J. R. Metabolite analysis of biological fluids and tissues by proton nuclear magnetic resonance spectroscopy. In Metabolomics Tools for Natural Product Discovery 81–97 (Springer, 2013).
  14. Smolinska A., Blanchet L., Buydens L. M. C. & Wijmenga S. S. NMR and pattern recognition methods in metabolomics: from data acquisition to biomarker discovery: a review. Anal. Chim. Acta 750: 82–97 (2012).
  15. Sreedhar A. & Zhao Y. Dysregulated metabolic enzymes and metabolic reprogramming in cancer cells. Biomed. Reports 8: 3–10 (2018).
  16. Warburg O. On the origin of cancer cells. Science (80-. ). 123: 309–314 (1956).
  17. Shan C., Lu Z., Sheng H., Fan J., Qi Q., Liu S., Zhang S. 4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis. Cell Death Dis. 10: 525 (2019).
  18. Halama A., Guerrouahen BS., Pasquier J., Diboun I., Karoly ED., Suhre K., Rafii A. Metabolic signatures differentiate ovarian from colon cancer cell lines. J. Transl. Med. 13: 223 (2015).
  19. Kaji M., Kabir-Salmani M., Anzai N., Jin CJ., Akimoto Y., Horita A., Sakamoto A., Kanai Y., Sakurai H., Iwashita M. Properties of L-type amino acid transporter 1 in epidermal ovarian cancer. Int. J. Gynecol. Cancer 20: 329–336 (2010).
  20. Aird K. M. & Zhang R. Nucleotide metabolism, oncogene-induced senescence, and cancer. Cancer Lett. 356: 204–210 (2015).
  21. Rizzo A., Napoli A., Roggiani F., Tomassetti A., Bagnoli M., Mezzanzanica D. One-carbon metabolism: biological players in epithelial ovarian cancer. Int. J. Mol. Sci. 19: 2092 (2018).
  22. Garg G., Yilmaz A., Kumar P., Turkoglu O., Mutch DG., Powell MA., Rosen B., Bahado-Singh RO., Graham SF. Targeted metabolomic profiling of low and high grade serous epithelial ovarian cancer tissues: a pilot study. Metabolomics 14: 154 (2018).
  23. Kisková T. & Kassayová M. Resveratrol Action on Lipid Metabolism in Cancer. Int. J. Mol. Sci. 20: 2704 (2019).
  24. Yu X., Ren X., Liang X. & TangY. Roles of fatty acid metabolism in tumourigenesis: Beyond providing nutrition. Mol. Med. Rep. 18: 5307–5316 (2018).
  25. UedaS M., Yap KL., Davidson B., Tian Y., Murthy V., Wang TL., Visvanathan K., Kuhajda FP., Bristow RE., Zhang H., Shih IeM. Expression of fatty acid synthase depends on NAC1 and is associated with recurrent ovarian serous carcinomas. J. Oncol. 2010. (2010).
  26. Ricciardi M. R., Mirabilii S., Allegretti M., Licchetta R., Calarco A., Torrisi MR, Foà R., Nicolai R., Peluso G., Tafuri A. Targeting the leukemia cell metabolism by the CPT1a inhibition: functional preclinical effects in leukemias. Blood 126:1925–1929 (2015).
  27. Amézaga J., Arranz S., Urruticoechea A., Ugartemendia G., Larraioz A., Louka M., Uriarte M., Ferreri C. Tueros Altered Red Blood Cell Membrane Fatty Acid Profile in Cancer Patients. Nutrients 10: 1853 (2018).
  28. Flavin R., Peluso S., Nguyen P. L. & Loda M. Fatty acid synthase as a potential therapeutic target in cancer. Futur. Oncol. 6: 551–562 (2010).
  29. Zeleznik O. A., Eliassen H., Kraft P., Poole E.M., Rosner B., Jeanfavre S., Deik A., Bullock K., Hitchcock D., Avila-Pancheco J., Clish C.B., Tworoger S.S. A prospective analysis of circulating plasma metabolomics and ovarian cancer risk. bioRxiv 654962 (2019).
  30. Hirasawa A., Makita K., Akahane T., Yokota M., Yamagami W., Banno K., Susumu N., and Aoki D.Hypertriglyceridemia is frequent in endometrial cancer survivors. Jpn. J. Clin. Oncol. 43: 1087–1092 (2013).

 
  1. Tulinius H., Sigfússon N., Sigvaldason H., Bjarnadóttir K. & Tryggvadottir L. Risk factors for malignant diseases: a cohort study on a population of 22,946 Icelanders. Cancer Epidemiol. Prev. Biomarkers 6: 863–873 (1997).
  2. Long J., Zhang C.J., Zhu N., Du K.,Yin Y.F., Tan X., Lio D.F., and Qin L. Lipid metabolism and carcinogenesis, cancer development. Am. J. Cancer Res. 8: 778 (2018).
Journal of Sciences, Islamic Republic of Iran
Volume 31, Issue 3
Summer 2020
Pages 205-212