Effects of coadministration of artemisinin and iron on histopathological alterations in the AGS gastric adenocarcinoma cell line

Effects of coadministration of artemisinin and iron on histopathological alterations in the AGS gastric adenocarcinoma cell line

Background/aim: The aim of the present study was to examine the anticancer effects of combination treatment with artemisinin and iron on the human gastric cancer cell line. Materials and methods: The AGS cell line was cultivated separately as a monolayer in culture flasks and different doses of 99% pure artemisinin with invariable doses of iron sulfate were added to the culture media and adhesive cells on the flask s bottom were stained with hematoxylin eosin for a pathological assay. Results: Damage to cancerous cells increased dose dependently and it was higher in the combination treatment groups (artemisinin plus iron). The histopathological changes were observed specially in the groups with high artemisinin concentration as cell swelling, nucleus swelling, and formation of small and large vacuolization. Necrotic changes as nucleus pyknosis were seen too. Changes in groups receiving both artemisinin and iron gradually became more severe with dose increase. Conclusion: Pathologic studies showed that the cytotoxic effects of artemisinin were dose dependent and the presence of iron enhanced the artemisinin s anticancer potency.

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  • 1. Lombard M, N’Da D, Breytenbach J, Kolesnikova N, Tran VBC, Wein S. Antimalarial and anticancer activities of artemisinin quinoline hybrid dimers and pharmacokinetic properties in mice. Eur J Pharm Sci 2012; 47: 834-841.
  • 2. Lai H, Singh N, Sasaki T. Development of artemisinin compounds for cancer treatment. Invest New Drugs 2013; 31: 230-246.
  • 3. Shahbazfar A, Zare P, Mohammadpour H, Tayefi NH. Effects of different concentrations of artemisinin and artemisinin iron combination treatment on Madin Darby Canine Kidney (MDCK) cells. Interdiscip Toxicol 2012; 5: 30-37.
  • 4. Sundar SN, Marconett CN, Doan VB, Willoughby JA Sr, Firestone GL. Artemisinin selectively decreases functional levels of estrogen receptor-alpha and ablates estrogen-induced proliferation in human breast cancer cells. Carcinogenesis 2008; 29: 2252-2258.
  • 5. Shahbazfar AA, Zare P, Ranjbaran M, Tayefi Nasrabadi H, Fakhri O, Farshi Y, Shadi S, Khoshkerdar A. A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 5637 (bladder cancer) and 4t1 (breast cancer) cell lines. J Cancer Res Ther 2014; 10: 1057-1062.
  • 6. Gao W, Xiao F, Wang X, Chen T. Artemisinin induces a549 cell apoptosis dominantly via a reactive oxygen species mediated amplification activation loop among caspase 9, 8 and 3. Apoptosis 2013; 18: 1201-1213.
  • 7. Zhang YJ, Gallis B, Taya M, Wang S, Ho RJ, Sasaki T. pHresponsive artemisinin derivatives and lipid nanoparticle formulations inhibit growth of breast cancer cells in vitro and induce down regulation of her family members. PloS one 2013; 8: e59086.
  • 8. Lai H, Sasaki T, Singh NP, Messay A. Effects of artemisinintagged holotransferrin on cancer cells. Life Sciences 2005; 76: 1267-1279.
  • 9. Cheng R, Li C, Wei L, Li L, Zhang Y, Yao Y, Gu X, Cai W, Yang Z, Gao G. The artemisinin derivative artesunate inhibits corneal neovascularization by inducing ROS-dependent apoptosis in vascular endothelial cells. Invest Ophthalmol Vis Sci 2013; 54: 3400-3409.
  • 10. Liu JJ, Fei AM, Nie RM, Wang J, Li Y, Wang ZY, Mi JQ. A new artemisinin derivative SM1044 induces apoptosis of Kasumi 1 cells and its mechanism. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2011; 19: 607-611.
  • 11. Zhang S, Gerhard GS. Heme activates artemisinin more efficiently than hemin, inorganic iron, or hemoglobin. Bioorg Med Chem 2008; 16: 7853-7861.
  • 12. Efferth T, Benakis A, Romero MR, Tomicic M, Rauh R, Steinbach D, Häfer R, Stamminger T, Oesch F, Kaina B et al. Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron. Free Radic Biol Med 2004; 37: 998-1009.
  • 13. Xiao F, Gao W, Wang X, Chen T. Amplification activation loop between caspase 8 and 9 dominates artemisinin induced apoptosis of ASTC-a-1 cells. Apoptosis 2012; 17: 600-611.
  • 14. Karagozlu MZ, Karadeniz F, Kong CS, Kim SK. Aminoethylated chitooligomers and their apoptotic activity on AGS human cancer cells. Carbohydrate Polymers 2012; 87: 1383-1389.
  • 15. Yuan CX, Zhou ZW, Yang YX, He ZX, Zhang X, Wang D, Yang T, Wang NJ, Zhao RJ, Zhou SF. Inhibition of mitotic Aurora kinase A by alisertib induces apoptosis and autophagy of human gastric cancer AGS and NCI-N78 cells. Drug Des Devel Ther 2015; 9: 487-508.
  • 16. Nakase I, Gallis B, Takatani-Nakase T, Oh S, Lacoste E, Singh NP, Goodlett DR, Tanaka S, Futaki S, Lai H et al. Transferrin receptor dependent cytotoxicity of artemisinin transferrin conjugates on prostate cancer cells and induction of apoptosis. Cancer Lett 2009; 274: 290-298.
  • 17. Lai H, Nakase I, Lacoste E, Singh NP, Sasaki T. Artemisinintransferrin conjugate retards growth of breast tumors in the rat. Anticancer Res 2009; 29: 3807-3810.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
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