The Potential of 9,10-Anthraquinone in Inhibiting Human Cancer Cells Growth
Background: 9,10-Anthraquinone (9,10-AQ) is a contaminant on some agricultural products and considered as carcinogenic based on EU Regulation No. 1146/2014. Except for little evidence on experimental rats, there is no strong proof regarding the carcinogenicity in humans. Therefore, it is essential to find a safe dose of this compound since the difference in 9,10-AQ levels will affect cancer cell growth. This research aims to find the 9,10-AQ concentration that does not proliferate the human cancer cells under in vitro study.
Methods: In determining the 9,10-AQ concentration that does not proliferate the cancer cells growth, 0.01 to 500 mg/L 9,10-AQ was directly tested on four human cancer cells (colorectal carcinoma HCT 116, colon adenocarcinoma WiDr, breast cancer MCF-7, and cervical cancer HeLa), and the viability of the cells was counted via (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. In the gene expression level, the effects on a selected cancer cell line were determined by qRT-PCR against BAX, BCL-2, PCNA, and P53.
Results: The result indicates that 9,10-AQ up to 500 mg/L concentration does not proliferate the cell’s growth but instead inhibits those four cancer cells’ growths. The concentration of 9,10-AQ that inhibits 50% the cancer cells growth (IC50) value was 321.8 mg/L (1.55 mM) against HCT 116 and above 500 mg/L (above 2.40 mM) against WiDr, MCF-7, and HeLa. The 9,10-AQ at 500 mg/L (or 2.40 mM) increases BAX expression and acts as an apoptotic agent on HeLa cells.
Conclusions: The investigation has shown that 9,10-AQ up to 500 mg/L concentration does not proliferate the cancer cell growth; instead, it inhibits the HCT 116 and HeLa cells growth. We have preliminary evidence regarding the apoptotic mechanism of 9,10-AQ by increasing BAX gene expression on HeLa cells.
DeLiberto ST, Werner SJ. Review of anthraquinone applications for pest management and agricultural crop protection. Pest Manag Sci. 2016;72(10):1813–25.
Food E, Authority S. Reasoned opinion on the review of the existing maximum residue levels (MRLs) for anthraquinone according to Article 12 of Regulation (EC) No 396/2005. EFSA J. 2012;10(6):6–11.
EFSA. Scientific opinion on pyrrolizidine alkaloids in food and feed: EFSA Panel on Contaminants in the Food Chain (CONTAM). EFSA J [Internet]. 2011;9(11):1–134. Available from: c:%5CUsers%5CJames%5CDocuments%5CDropbox%5CLiteratura-PDF%5CBiblio PAs%5CEFSA2011.pdf
European Chemicals Agency. Guidance on the Application of the CLP Criteria [Internet]. European Chemicals Agency; 2017. 1–647 p. Available from: https://echa.europa.eu/documents/10162/23036412/clp_en.pdf
O’Donoghue JL. Neurotoxicity of industrial and commercial chemicals. Vol.1. 1st ed. Boca Raton: CRC; 1985.
Merck. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th ed. O’Neil MJ, Smith A, Heckelman PE BS, editor. Whitehouse Station, NJ, USA; 2001.
Sylvester PW. Optimization of the tetrazolium dye (MTT) colorimetric assay for cellular growth and viability. Methods Mol Biol. 2011;716(July):157–68.
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3(6):1101–8.
Hussain H, Al-Harrasi A, Al-Rawahi A, et al. A fruitful decade from 2005 to 2014 for anthraquinone patents. Expert Opin Ther Pat. 2015;25(9):1053–64.
Crowley LC, Marfell BJ, Scott AP, et al. Dead cert: Measuring cell death. Cold Spring Harb Protoc. 2016;2016(12):1064–72.
Flanagan L, Lindner AU, de Chaumont C, et al. BCL2 protein signalling determines acute responses to neoadjuvant chemoradiotherapy in rectal cancer. J Mol Med. 2015;93(3):315–26.
Nolte E, Sobel A, Wach S, et al. The new semisynthetic cardenolide analog 3β-[2-(1-Amantadine)-1-on-ethylamine]-digitoxigenin (AMANTADIG) efficiently suppresses cell growth in human leukemia and urological tumor cell lines. Anticancer Res. 2015;35(10):5271–6.
Doi AM, Irwin RD, Bucher JR. Influence of functional group substitutions on the carcinogenicity of anthraquinone in rats and mice: Analysis of long-term bioassays by the National Cancer Institute and the National Toxicology Program. J Toxicol Environ Heal - Part B Crit Rev. 2005;8(2):109–26.
Public Health Service. NTP Technical Report on the Toxicology and Carcinogenesis Studies of Primidone ( Feed Studies ) National Toxicology Program [Internet]. Vol. NTP TR 494. North Columbia; 2005. Available from: http://eds.a.ebscohost.com.ezproxy.endeavour.edu.au/eds/pdfviewer/pdfviewer?sid=1e83dda5-700a-4db9-9540f3b04ec02cd6@sessionmgr4004&vid=8&hid=4205
Shin J, Seol I, Son C. Interpretation of Animal Dose and Human Equivalent Dose for Drug Development. J Korean Orient Med. 2010;31(3):1–7.
Wooltorton E. Too much of a good thing? Toxic effects of vitamin and mineral supplements. Cmaj. 2003;169(1):47–8.
Convertino M, Pellarin R, Catto M, et al. 9,10-Anthraquinone hinders β-aggregation: How does a small molecule interfere with Aβ-peptide amyloid fibrillation? Protein Sci. 2009;18(4):792–800.
Wahyuningsih MSH, Mubarika S, Ganjar IG, et al. 5α-Oleandrin reduce Bcl-2 protein and increase Bax protein expression on Hela cervical cancer cell. Universa Med. 2017;36(2):102.
Long L, Li Q. The effect of alkaloid from Oxytropis ochrocephala on growth inhibition and expression of PCNA and p53 in mice bearing H22 hepatocellular carcinoma. Yakugaku Zasshi. 2005;125(8):665–70.
Lu Z, Xiao Y, Liu X, et al. Matrine reduces the proliferation of A549 cells via the p53/p21/PCNA/eIF4E signaling pathway. Mol Med Rep. 2017;15(5):2415–22.
Farnebo M, Bykov VJN, Wiman KG. The p53 tumor suppressor: A master regulator of diverse cellular processes and therapeutic target in cancer. Biochem Biophys Res Commun. 2010;396(1):85–9.
Pflaum J, Schlosser S, Müller M. P53 family and cellular stress responses in cancer. Front Oncol. 2014;4(OCT):1–15.
Article MetricsAbstract view : 44 times
PDF - 34 times
- There are currently no refbacks.
Copyright (c) 2021 Indonesian Journal of Cancer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.