Skip to main content

Advertisement

SpringerLink
Log in

Curcumin-Induced DNA Damage and Inhibited DNA Repair Genes Expressions in Mouse–Rat Hybrid Retina Ganglion Cells (N18)

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Curcumin is reported to be a potent inhibitor of the initiation and promotion of many cancer cells. We investigated to examine whether or not curcumin induce DNA damage in mouse–rat hybrid retina ganglion cell line N18 cells. The Comet assay showed that incubation of N18 cells with 10, 25 and 30 μM of curcumin led to a longer DNA migration smear (Comet tail). The DNA gel electrophoresis showed that 20 μM of curcumin for 24 and 48 h treatment induced DNA damage and fragments in N18 cells. The real time PCR analysis showed that 20 μM of curcumin for 48 h treatment decreased ATM, ATR, BRCA1, 14-3-3σ, DNA-PK and MGMT mRNA, and ATM and MGMT mRNA expression were inhibited in a time-dependent manner. Our results indicate that curcumin caused DNA damage and inhibited DNA repair genes which may be the factors for curcumin-inhibited cell growth.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Karunagaran D, Rashmi R, Kumar TR (2005) Induction of apoptosis by curcumin and its implications for cancer therapy. Curr Cancer Drug Targets 5:117–129. doi:10.2174/1568009053202081

    Article  PubMed  CAS  Google Scholar 

  2. Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV et al (1999) Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res 59:597–601

    PubMed  CAS  Google Scholar 

  3. Chuang SE, Kuo ML, Hsu CH, Chen CR, Lin JK, Lai GM et al (2000) Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis. Carcinogenesis 21:331–335. doi:10.1093/carcin/21.2.331

    Article  PubMed  CAS  Google Scholar 

  4. Li N, Chen X, Liao J, Yang G, Wang S, Josephson Y et al (2002) Inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters by tea and curcumin. Carcinogenesis 23:1307–1313. doi:10.1093/carcin/23.8.1307

    Article  PubMed  CAS  Google Scholar 

  5. Bhandarkar SS, Arbiser JL (2007) Curcumin as an inhibitor of angiogenesis. Adv Exp Med Biol 595:185–195. doi:10.1007/978-0-387-46401-5_7

    Article  PubMed  Google Scholar 

  6. Aggarwal BB, Shishodia S, Takada Y, Banerjee S, Newman RA, Bueso-Ramos CE et al (2005) Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res 11:7490–7498. doi:10.1158/1078-0432.CCR-05-1192

    Article  PubMed  CAS  Google Scholar 

  7. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS et al (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21:2895–2900

    PubMed  CAS  Google Scholar 

  8. Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL et al (2008) Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 14:4491–4499. doi:10.1158/1078-0432.CCR-08-0024

    Article  PubMed  CAS  Google Scholar 

  9. Mullaart E, Boerrigter ME, Ravid R, Swaab DF, Vijg J (1990) Increased levels of DNA breaks in cerebral cortex of Alzheimer’s disease patients. Neurobiol Aging 11:169–173. doi:10.1016/0197-4580(90)90542-8

    Article  PubMed  CAS  Google Scholar 

  10. Adamec E, Vonsattel JP, Nixon RA (1999) DNA strand breaks in Alzheimer’s disease. Brain Res 849:67–77. doi:10.1016/S0006-8993(99)02004-1

    Article  PubMed  CAS  Google Scholar 

  11. Urbina-Cano P, Bobadilla-Morales L, Ramirez-Herrera MA, Corona-Rivera JR, Mendoza-Magana ML, Troyo-Sanroman R et al (2006) DNA damage in mouse lymphocytes exposed to curcumin and copper. J Appl Genet 47:377–382

    PubMed  Google Scholar 

  12. Cao J, Jia L, Zhou HM, Liu Y, Zhong LF (2006) Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells. Toxicol Sci 91:476–483. doi:10.1093/toxsci/kfj153

    Article  PubMed  CAS  Google Scholar 

  13. Nair J, Strand S, Frank N, Knauft J, Wesch H, Galle PR et al (2005) Apoptosis and age-dependant induction of nuclear and mitochondrial etheno-DNA adducts in Long-Evans Cinnamon (LEC) rats: enhanced DNA damage by dietary curcumin upon copper accumulation. Carcinogenesis 26:1307–1315. doi:10.1093/carcin/bgi073

    Article  PubMed  CAS  Google Scholar 

  14. Ahsan H, Hadi SM (1998) Strand scission in DNA induced by curcumin in the presence of Cu(II). Cancer Lett 124:23–30. doi:10.1016/S0304-3835(97)00442-4

    Article  PubMed  CAS  Google Scholar 

  15. Lin HL, Yang JS, Yang JH, Fan SS, Chang WC, Li YC et al (2006) The role of Ca2+ on the DADS-induced apoptosis in mouse–rat hybrid retina ganglion cells (N18). Neurochem Res 31:383–393. doi:10.1007/s11064-005-9035-1

    Article  PubMed  CAS  Google Scholar 

  16. Hsu SC, Kuo CL, Lin JP, Lee JH, Lin CC, Su CC et al (2007) Crude extracts of Euchresta formosana radix inhibit invasion and migration of human hepatocellular carcinoma cells. Anticancer Res 27:2377–2384

    PubMed  CAS  Google Scholar 

  17. Lee JH, Li YC, Ip SW, Hsu SC, Chang NW, Tang NY et al (2008) The role of Ca2+ in baicalein-induced apoptosis in human breast MDA-MB-231 cancer cells through mitochondria- and caspase-3-dependent pathway. Anticancer Res 28:1701–1711

    PubMed  CAS  Google Scholar 

  18. Chen JC, Lu KW, Tsai ML, Hsu SC, Kuo CL, Yang JS et al. (2008) Gypenosides induced G0/G1 arrest via CHk2 and apoptosis through endoplasmic reticulum stress and mitochondria-dependent pathways in human tongue cancer SCC-4 cells. Oral Oncol 45:273–283

    Google Scholar 

  19. Ip SW, Liao SS, Lin SY, Lin JP, Yang JS, Lin ML et al (2008) The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells. In Vivo 22:237–245

    PubMed  Google Scholar 

  20. Hsu SC, Kuo CL, Lin JP, Lee JH, Lin CC, Su CC et al (2007) Crude extracts of Euchresta formosana radix induce cytotoxicity and apoptosis in human hepatocellular carcinoma cell line (Hep3B). Anticancer Res 27:2415–2425

    PubMed  CAS  Google Scholar 

  21. Hsu MH, Chen CJ, Kuo SC, Chung JG, Lai YY, Teng CM et al (2007) 2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1) induces mitotic phase arrest in A549 cells. Eur J Pharmacol 559:14–20. doi:10.1016/j.ejphar.2006.12.001

    Article  PubMed  CAS  Google Scholar 

  22. Lin JG, Chen GW, Li TM, Chouh ST, Tan TW, Chung JG (2006) Aloe-emodin induces apoptosis in T24 human bladder cancer cells through the p53 dependent apoptotic pathway. J Urol 175:343–347. doi:10.1016/S0022-5347(05)00005-4

    Article  PubMed  CAS  Google Scholar 

  23. Lu KH, Lue KH, Chou MC, Chung JG (2005) Paclitaxel induces apoptosis via caspase-3 activation in human osteogenic sarcoma cells (U-2 OS). J Orthop Res 23:988–994. doi:10.1016/j.orthres.2005.01.018

    Article  PubMed  CAS  Google Scholar 

  24. Lin SS, Huang HP, Yang JS, Wu JY, Hsai TC, Lin CC et al. (2008) DNA damage and endoplasmic reticulum stress mediated curcumin-induced cell cycle arrest and apoptosis in human lung carcinoma A-549 cells through the activation caspases cascade- and mitochondrial-dependent pathway. Cancer lett 272:77–90

    Google Scholar 

  25. Ashby J, Tinwell H, Lefevre PA, Browne MA (1995) The single cell gel electrophoresis assay for induced DNA damage (comet assay): measurement of tail length and moment. Mutagenesis 10:85–90. doi:10.1093/mutage/10.2.85

    Article  PubMed  CAS  Google Scholar 

  26. Pool-Zobel BL, Lotzmann N, Knoll M, Kuchenmeister F, Lambertz R, Leucht U et al (1994) Detection of genotoxic effects in human gastric and nasal mucosa cells isolated from biopsy samples. Environ Mol Mutagen 24:23–45. doi:10.1002/em.2850240105

    Article  PubMed  CAS  Google Scholar 

  27. Donatus IA, Sardjoko Vermeulen NP (1990) Cytotoxic and cytoprotective activities of curcumin. Effects on paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion in rat hepatocytes. Biochem Pharmacol 39:1869–1875. doi:10.1016/0006-2952(90)90603-I

    Article  PubMed  CAS  Google Scholar 

  28. Tice RR, Andrews PW, Singh NP (1990) The single cell gel assay: a sensitive technique for evaluating intercellular differences in DNA damage and repair. Basic Life Sci 53:291–301

    PubMed  CAS  Google Scholar 

  29. Olive PL, Banath JP, Durand RE (1990) Detection of etoposide resistance by measuring DNA damage in individual Chinese hamster cells. J Natl Cancer Inst 82:779–783. doi:10.1093/jnci/82.9.779

    Article  PubMed  CAS  Google Scholar 

  30. Sahu SC, Washington MC (1992) Effect of ascorbic acid and curcumin on quercetin-induced nuclear DNA damage, lipid peroxidation and protein degradation. Cancer Lett 63:237–241. doi:10.1016/0304-3835(92)90266-X

    Article  PubMed  CAS  Google Scholar 

  31. Chakraborty S, Roy M, Bhattacharya RK (2004) Prevention and repair of DNA damage by selected phytochemicals as measured by single cell gel electrophoresis. J Environ Pathol Toxicol Oncol 23:215–226. doi:10.1615/JEnvPathToxOncol.v23.i3.50

    Article  PubMed  CAS  Google Scholar 

  32. Hanif R, Qiao L, Shiff SJ, Rigas B (1997) Curcumin, a natural plant phenolic food additive, inhibits cell proliferation and induces cell cycle changes in colon adenocarcinoma cell lines by a prostaglandin-independent pathway. J Lab Clin Med 130:576–584. doi:10.1016/S0022-2143(97)90107-4

    Article  PubMed  CAS  Google Scholar 

  33. Jiang MC, Yang-Yen HF, Yen JJ, Lin JK (1996) Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. Nutr Cancer 26:111–120

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Grant NSC 95-2745-B-039-002-URD from the National Science Council of Taiwan.

Author information

Authors and Affiliations

  1. Department of Clinical Pathology, Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan, ROC

    Hsu-Feng Lu & Shu-Ching Hsueh

  2. Department of Pharmacology, China Medical University, Taichung, Taiwan, ROC

    Jai-Sing Yang

  3. Department of Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan, ROC

    Kuang-Chi Lai

  4. Institute of Chinese Pharmaceutical Sciences, China Medical University, Taichung, Taiwan, ROC

    Shu-Chun Hsu

  5. Department of Medical Technology, Yuan-Pei Institute of Science and Technology, Hsinchu, Taiwan, ROC

    Yuan-Liang Chen

  6. Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, ROC

    Jo-Hua Chiang & Chi-Cheng Lu

  7. School of Nursing, Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan, ROC

    Chyi Lo

  8. Department of Surgery, China Medical University Hospital, Taichung, Taiwan, ROC

    Mei-Due Yang

  9. Department of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung, 404, Taiwan, ROC

    Jing-Gung Chung

  10. Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan, ROC

    Jing-Gung Chung

Authors
  1. Hsu-Feng Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jai-Sing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kuang-Chi Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shu-Chun Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shu-Ching Hsueh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuan-Liang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jo-Hua Chiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chi-Cheng Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chyi Lo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mei-Due Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jing-Gung Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jing-Gung Chung.

Additional information

H.-F. Lu and J.-S. Yang are contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lu, HF., Yang, JS., Lai, KC. et al. Curcumin-Induced DNA Damage and Inhibited DNA Repair Genes Expressions in Mouse–Rat Hybrid Retina Ganglion Cells (N18). Neurochem Res 34, 1491–1497 (2009). https://doi.org/10.1007/s11064-009-9936-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-009-9936-5

Keywords

Search

Navigation