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Journal of Neuro-Oncology

, Volume 74, Issue 2, pp 105–111 | Cite as

Inhibition of Cellular Proliferation and Induction of Apoptosis by Curcumin in Human Malignant Astrocytoma Cell Lines

  • Shoichi NagaiEmail author
  • Masanori Kurimoto
  • Kazuo Washiyama
  • Yutaka Hirashima
  • Toshiro Kumanishi
  • Shunro Endo
Laboratory Investigation

Summary

Nuclear factor (NF)-κB is known to control cellular proliferation and apoptosis. In malignant astrocytoma cells, it was reported that NF-κB was activated aberrantly and promoted their proliferation. Thus, inhibition of NF-κB activity is considered to be a promising therapeutic strategy for malignant astrocytoma. Recently, curcumin, the major constituent of turmeric, was reported to inhibit NF-κB activity. In this study, we investigated inhibitory effects of curcumin on NF-κB activity and cellular proliferation, and induction of apoptosis by curcumin in human malignant astrocytoma cell lines. Alteration of NF-κB activity in NP-2 human malignant astrocytoma cell line after treatment with curcumin was examined using electrophoretic mobility shift assay. Alterations of DNA synthesis and cellular growth in five human malignant astrocytoma cell lines after treatment with curcumin were examined using [3H]thymidine incorporation assay and the trypan blue dye exclusion method, respectively. Induction of apoptosis by curcumin in NP-2 and NP-3 human malignant astrocytoma cell lines was examined by DNA-fragmentation analysis and morphological observation. We found that the NF-κB activity in NP-2 was significantly reduced by curcumin. The DNA synthesis and the cellular growth were inhibited by curcumin in dose-dependent manner in all the five malignant astrocytoma cell lines. Nuclear condensation and fragmentation, and DNA fragmentation were observed in both NP-2 and NP-3 after the treatment with curcumin. These results indicate that curcumin inhibits the cellular proliferation and induces apoptosis in human malignant astrocytoma cell lines. These results are considered to be resulted from the inhibition of NF-κB activity by curcumin.

Keywords

apoptosis curcumin growth inhibition malignant astrocytoma nuclear factor-κ

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References

  1. 1.
    Yamamoto, Y, Gaynor, RB 2001Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancerJ Clin Invest107135142PubMedGoogle Scholar
  2. 2.
    Schwartz, SA, Hernandez, A, Mark Evers, B 1999The role of NF-κB/IκB proteins in cancer: implications for novel treatment strategiesSurg Oncol8143153CrossRefPubMedGoogle Scholar
  3. 3.
    Chen, F, Castranova, V, Shi, X 2001New insights into the role of nuclear factor-κB in cell growth regulationAm J Pathol159387397PubMedGoogle Scholar
  4. 4.
    Hinz, M, Krappmann, D, Eichten, A, Heder, A, Scheidereit, C, Strauss, M 1999NF-κB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transitionMol Cell Biol1926902698PubMedGoogle Scholar
  5. 5.
    Beg, AA, Sha, WC, Bronson, RT, Ghosh, S, Baltimore, D 1995Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κBNature376167170CrossRefPubMedGoogle Scholar
  6. 6.
    Beg, AA, Baltimore, D 1996An essential role for NF-κB in preventing TNF-α-induced cell deathScience274782784Google Scholar
  7. 7.
    Lantos, PL, VandenBerg, SR, Kleihues, P 1997Tumors of the nervous systemGraham, DILantos, PL eds. Greenfield’s Neuropathology6ArnoldLondon583879Vol 2Google Scholar
  8. 8.
    Nagai, S, WashiyamaK. Kurimoto, M, Takaku, A, Endo, S, Kumanishi, T 2002Aberrant nuclear factor-κB activity and its participation in the growth of human malignant astrocytomaJ Neurosurg96909917PubMedGoogle Scholar
  9. 9.
    Singh, S, Aggarwal, BB 1995Activation of transcription factor NF-κB is suppressed by curcumin (diferuloylmethane)J Biol Chem2702499525000CrossRefPubMedGoogle Scholar
  10. 10.
    Jobin, C, Bradham, CA, Russo, MP, Juma, B, Narula, AS, Brenner, DA, Sartor, RB 1999Curcumin blocks cytokine-mediated NF-κB activation and proinflammatory gene expression by inhibiting inhibitory factor I-κB kinase activityJ Immunol16334743483PubMedGoogle Scholar
  11. 11.
    Ammon, HPT, Wahl, MA 1991Pharmacology of curcuma longaPlanta Med5717PubMedGoogle Scholar
  12. 12.
    Hanif, R, Qiao, L, Shiff, SJ, Rigas, B 1997Curcumin, a natural plant phenolic food additive, inhibits cell proliferation and induces cell cycle changes in colon adenocarcinoma cell lines by a prostaglandin-independent pathwayJ Lab Clin Med130576584CrossRefPubMedGoogle Scholar
  13. 13.
    Mehta, K, Pantazis, P, McQueen, T, Aggarwal, BB 1997Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell linesAnti-Cancer Drugs8470481PubMedGoogle Scholar
  14. 14.
    Aggarwal, BB, Kumar, A, Bharti, AC 2003Anticancer potential of␣curcumin: Preclinical and clinical studiesAnticancer Res23363398PubMedGoogle Scholar
  15. 15.
    Frautschy, SA, Hu, W, Kim, P, Miller, SA, Chu, T, Harris-White, ME, Cole, GM 2001Phenolic anti-imflammatory antioxidant reversal of Aβ-induced cognitive deficits and neuropathologyNeurobiol Aging229931005CrossRefPubMedGoogle Scholar
  16. 16.
    Ghoneim, AI, Abdel-Naim, AB, Khalifa, AE, El-Denshary, ES 2002Protective effects of curcumin against ischaemia/reperfusion insult in rat forebrainPharmacol Res46273279CrossRefPubMedGoogle Scholar
  17. 17.
    Lim, GP, Chu, T, Yang, F, Beech, W, Frautschy, SA, Cole, GM 2001The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouseJ Neurosci2183708377PubMedGoogle Scholar
  18. 18.
    Rajakrishnan, V, Viswanathan, P, Rajasekharan, KN, Menon, VP 1999Neuroprotective role of curcumin from Curcuma longa on ethanol-induced brain damagePhytother Res13571574CrossRefPubMedGoogle Scholar
  19. 19.
    Shukla, PK, Khanna, VK, Khan, MY, Srimal, RC 2003Protective effect of curcumin against lead neurotoxicity in ratHum Exp Toxicol22653658CrossRefPubMedGoogle Scholar
  20. 20.
    Thiyagarajan, M, Sharma, SS 2004Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in ratsLife Sci74969985CrossRefPubMedGoogle Scholar
  21. 21.
    Vajragupta, O, Boonchoong, P, Watanabe, H, Tohda, M, Kummasud, N, Sumanont, Y 2003Manganese complexes of curcumin and its derivatives: evaluation for the radical scavenging ability and neuroprotective activityFree Radic Biol Med3516321644CrossRefPubMedGoogle Scholar
  22. 22.
    Huang, MT, Lou, YR, Ma, W, Newmark, HL, Reuhl, KR, Conney, AH 1994Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in miceCancer Res5458415847PubMedGoogle Scholar
  23. 23.
    Huang, MT, Smart, RC, Wong, CQ, Conney, AH 1988Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetateCancer Res4859415946PubMedGoogle Scholar
  24. 24.
    Rao, CV, Rivenson, A, Simi, B, Reddy, BS 1995Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compoundCancer Res55259266PubMedGoogle Scholar
  25. 25.
    Anto, RJ, Maliekal, TT, Karunagaran, D 2000L-929 cells harboring ectopically expressed RelA resist curcumin-induced apoptosisJ Biol Chem2751560115604CrossRefPubMedGoogle Scholar
  26. 26.
    Khar, A, Ali, AM, Pardhasaradhi, BVV, Begum, Z, Anjum, R 1999Antitumor activity of curcumin is mediated through the induction of apoptosis in AK-5 tumor cellsFEBS Lett445165168CrossRefPubMedGoogle Scholar
  27. 27.
    Onda, K, Nagai, S, Tanaka, R, Morii, K, Yoshimura, JI, Tsumanuma, I, Kumanishi, T 1999Establishment of two glioma cell lines from two surgical specimens obtained at different times from the same individualJ Neurooncol41247254CrossRefPubMedGoogle Scholar
  28. 28.
    Onda, K, Tanaka, R, Washiyama, K, Takeda, N, Kumanishi, T 1988Correlation of DNA ploidy and morphological features of human glioma cell cultures with the establishment of cell linesActa Neuropathol76433440CrossRefPubMedGoogle Scholar
  29. 29.
    Yamazaki, K 1982Tumorigenicity of established human glioma cell lines in lasat and nude miceNeuropathology32938(Jpn)Google Scholar
  30. 30.
    Kunsch, C, Ruben, SM, Rosen, CA 1992Selection of optimal κB/Rel DNA-binding motifs: interaction of both subunits of NF-κB with DNA is required for transcriptional activationMol Cell Biol1244124421PubMedGoogle Scholar
  31. 31.
    Mukhopadhyay, A, Banerjee, S, Stafford, LJ, Xia, C, Liu, M, Aggarwal, BB 2002Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediaated retinoblastoma protein phosphorylationOncogene2188528861CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Shoichi Nagai
    • 1
    • 2
    Email author
  • Masanori Kurimoto
    • 1
  • Kazuo Washiyama
    • 2
  • Yutaka Hirashima
    • 1
  • Toshiro Kumanishi
    • 2
  • Shunro Endo
    • 1
  1. 1.Department of NeurosurgeryToyama medical and Pharmaceutical UniversityToyamaJapan
  2. 2.Department of Molecular Neuropathology, Brain Research InstituteNiigata UniversityNiigataJapan

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