Gold Nanoparticles Enhance the Anticancer Activity of Gallic Acid against Cholangiocarcinoma Cell Lines

  • Rattanata, Narintorn (Department of Biochemistry, Faculty of Science, Khon Kaen University) ;
  • Daduang, Sakda (Faculty of Pharmaceutical Sciences, Khon Kaen University) ;
  • Wongwattanakul, Molin (Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University) ;
  • Leelayuwat, Chanvit (Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University) ;
  • Limpaiboon, Temduang (Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University) ;
  • Lekphrom, Ratsami (Department of Chemistry, Faculty of Science, Khon Kaen University) ;
  • Sandee, Alisa (Chulabhorn Research Institute) ;
  • Boonsiri, Patcharee (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Chio-Srichan, Sirinart (Synchrotron Light Research Institute (Public Organization)) ;
  • Daduang, Jureerut (Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University)
  • Published : 2015.11.04


Gold nanoparticles (GNPs) were conjugated with gallic acid (GA) at various concentrations between 30 and $150{\mu}M$ and characterized using transmission electron microscopy (TEM) and UV-Vis spectroscopy (UV-VIS). The anticancer activities of the gallic acid-stabilized gold nanoparticles against well-differentiated (M213) and moderately differentiated (M214) adenocarcinomas were then determined using a neutral red assay. The GA mechanism of action was evaluated using Fourier transform infrared (FTIR) microspectroscopy. Distinctive features of the FTIR spectra between the control and GA-treated cells were confirmed by principal component analysis (PCA). The surface plasmon resonance spectra of the GNPs had a maximum absorption at 520 nm, whereas GNPs-GA shifted the maximum absorption values. In an in vitro study, the complexed GNPs-GA had an increased ability to inhibit the proliferation of cancer cells that was statistically significant (P<0.0001) in both M213 and M214 cells compared to GA alone, indicating that the anticancer activity of GA can be improved by conjugation with GNPs. Moreover, PCA revealed that exposure of the tested cells to GA resulted in significant changes in their cell membrane lipids and fatty acids, which may enhance the efficacy of this anticancer activity regarding apoptosis pathways.


Gallic acid;gold nanoparticle;anticancer activity;cholangiocarcinoma;nanomedicine


  1. Borenfreund E and Puerner JA (1985). A simple quantitative procedure using monolayer cultures for cytotoxicity assays (HTD/NR-90). J Tissue Cult Met, 9, 7-9.
  2. Chandramohan RT, Bharat RD, Aparna A, et al (2012). Antileukemic effects of gallic acid on human leukemia K562 cells: downregulation of COX-2, inhibition of BCR/ABL kinase and NF-${\kappa}B$ inactivation. Toxicol In Vitro, 26, 396-405.
  3. Chithrani BD, Ghazani AA and Chan WC (2006). Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett, 6, 662-8.
  4. Daduang J, Palasap A, Daduang S, et al (2015). Gallic acid enhancement of gold nanoparticle anticancer activity in cervical cancer cells. Asian Pac J Cancer Prev, 16, 169-74.
  5. Gaudenzi S, Pozzi D, Toroa P, et al (2004). Cell apoptosis specific marker found by fourier transform infrared spectroscopy. Spectroscopy, 18, 415-22.
  6. Khan S, Davidson BR, Goldin R, et al (2002). Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document. Gut, 51, 1-9.
  7. Liao CL, Lai KC, Huang AC, et al. (2012). Gallic acid inhibits migration and invasion in human osteosarcoma U-2 OS cells through suppressing the matrix metalloproteinase-2/-9, protein kinase B (PKB) and PKC signaling pathways. Food Chem Toxicol, 50, 1734-40.
  8. Lu Y, Jiang F, Jiang H, et al (2010). Gallic acid suppresses cell viability, proliferation, invasion and angiogenesis in human glioma cells. Eur J Pharmacol, 641, 102-7.
  9. Mandal TK, Fleming MS and Walt DR (2002). Preparation of polymer coated gold nanoparticles by surface confined living radical polymerization at ambient temperature. Nano Lett, 2, 3-7.
  10. Mohamed MS, Veeranarayanan S, Poulose AC, et al (2014). Type 1 ribotoxin-curcin conjugated biogenic gold nanoparticles for a multimodal therapeutic approach towards brain cancer. Biochim Biophys Acta, 1840, 1657-69.
  11. Moreno-Alvarez SA, Martinez-Castanon GA, Nino-Martinez N; et al (2010). Preparation and bactericide activity of gallic acid stabilized gold nanoparticles. J Nanopart Res, 12, 2741-6.
  12. Ohno T, Inoue M and Ogihara Y (2001). Cytotoxic activity of gallic acid against liver metastasis of mastocytoma cells P-815. Anticancer Res, 21, 3875-80.
  13. Patra CR, Bhattacharya R, Wang E, et al (2008). Targeted delivery of gemcitabine to pancreatic adenocarcinoma using cetuximab as a targeting agent. Cancer Res, 68, 1970-8.
  14. Schug ZT, Gonzalvez F, Houtkooper RH,Vaz FM, Gottlieb E (2011). BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death Differ, 18, 538-48.
  15. Tepsiri N, Chaturat L, Sripa B, et al (2005). Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines. World J Gastroenterol, 11, 2748-53.
  16. Thongprasert S (2005). The role of chemotherapy in cholangiocarcinoma. Ann oncol, 16, 93-6.
  17. Turkevich J, Stevenson PC and Hillier J (1951). A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss. Faraday Soc, 11, 55-75.
  18. You BR, Moon HJ, Han YH, Park WH (2010). Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis. Food Chem Toxicol, 48, 1334-40.
  19. Zhao B and Hu M (2013). Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells. Oncol Lett, 6, 1749-55.

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