The Potential of 9,10-Anthraquinone in Inhibiting Human Cancer Cells Growth

Irmanida Batubara, Arif Rakhman Hakim, Silmi Mariya, Suminar Setiati Achmadi, Valentina Sokoastri, Agustin Sri Mulyatni, Rohayati Suprihatini

Abstract


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.


Keywords


anthraquinone, tea, human cancer cells, antiproliferation

References


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.


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DOI: 10.33371/ijoc.v15i1.780

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