Thymoquinone reduces migration and invasion of human glioblastoma cells associated with FAK, MMP-2 and MMP-9 down-regulation
- 768 Downloads
Glioblastoma represent the most frequent primary tumors of the central nervous system and remain among the most aggressive human cancers as available therapeutic approaches still fail to contain their invasiveness. Many studies have reported elevated expression of the Focal Adhesion Kinase (FAK) protein in glioblastoma, associated with an increase in the rates of both migration and invasion. This designates FAK as a promising target to limit invasiveness in glioblastoma. Thymoquinone (TQ), the main phytoactive compound of Nigella sativa has shown remarkable anti-neoplasic activities on a variety of cancer cells. Here, we studied the anti-invasive and anti-migratory effects of TQ on human glioblastoma cells. The results obtained indicated that TQ treatment reduced migration, adhesion and invasion of both U-87 and CCF-STTG1 cells. This was accompanied by a drastic down-regulation of FAK, associated with a reduction of ERK phosphorylation as well as MMP-2 and MMP-9 secretion. This study provides new data on FAK regulation by a natural product (TQ) which could be of a great value for the development of novel therapies in glioblastoma.
KeywordsFAK Thymoquinone Invasion Migration MMP Glioblastoma
This work was supported in part by grants from the Ligue Contre le Cancer (Comités de la région Alsace) to P. Rondé. K. Kolli-Bouhafs was supported by a doctoral fellowship from the Ministère de l’Enseignement et de la Recherche.
- 8.Natarajan M, Hecker TP, Gladson CL (2003) FAK signaling in anaplastic astrocytoma and glioblastoma tumors. Cancer journal (Sudbury, Mass 9 (2):126–133Google Scholar
- 10.Jones G, Machado J Jr, Tolnay M, Merlo A (2001) PTEN-independent induction of caspase-mediated cell death and reduced invasion by the focal adhesion targeting domain (FAT) in human astrocytic brain tumors which highly express focal adhesion kinase (FAK). Cancer Res 61(15):5688–5691PubMedGoogle Scholar
- 13.Padhye S, Banerjee S, Ahmad A, Mohammad R, Sarkar FH (2008) From here to eternity - the secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond. Canc Ther 6(b):495–510Google Scholar
- 16.Gali-Muhtasib H, Ocker M, Kuester D, Krueger S, El-Hajj Z, Diestel A, Evert M, El-Najjar N, Peters B, Jurjus A, Roessner A, Schneider-Stock R (2008) Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in murine colon cancer models. J Cell Mol Med 12(1):330–342PubMedCrossRefGoogle Scholar
- 30.Abusnina A, Alhosin M, Keravis T, Muller CD, Fuhrmann G, Bronner C, Lugnier C (2011) Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia cell apoptosis. Cell Signal 23(1):152–160PubMedCrossRefGoogle Scholar
- 37.Brunton VG, Avizienyte E, Fincham VJ, Serrels B, Metcalf CA 3rd, Sawyer TK, Frame MC (2005) Identification of Src-specific phosphorylation site on focal adhesion kinase: dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior. Cancer Res 65(4):1335–1342PubMedCrossRefGoogle Scholar
- 41.Yi T, Cho SG, Yi Z, Luo W, Wang Y, Sethi G, Aggarwal BB, Liu M (2008) Thymoquinone inhibits angiogenesis and prostate tumor growth by suppressing MAPK signaling pathways. The FASEB Journal 22:654.1Google Scholar
- 45.Singh G, Chan AM (2001) Post-translational modifications of PTEN and their potential therapeutic implications. Curr Cancer Drug Targets 11(5):536–47Google Scholar