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INHIBITION OF CELLULAR INVASION AND INDUCTION OF ANOIKIS IN MOUSE MELANOMA CELLS BY AN ANTI-INFLAMMATORY AGENT DTCM-GLUTARIMIDE

https://doi.org/10.24060/2076-3093-2012-0-3-4-9

Abstract

Previously, we designed DTCM-glutarimide as a novel anti-inflammatory agent inhibiting macrophage activation. It also showed anti-inflammatory activity in vivo. In the present research, we evaluated the  anti-metastatic activity of this agent using  mouse  melanoma B16-F10 cells. DTCM-glutarimide inhibited  the cellular invasion in the Matrigel chamber assay, lowering matrix metalloproteinase 9 (MMP9) expression. It also induced  anoikis rather than  apoptosis in polyHEMA-coated plates.  It increased Bax and decreased Bcl-XL  expressions,  and  activated p53  lowereing  the  MDM2 expression. Thus, DTCM-glutarimide was found to inhibit cellular invasion and to induce anoikis in B16-F10 cells. It is non-toxic, and easily prepared, therefore, is considered to be a new candidate of anti-metastasis agent.

About the Authors

A. Kaneda
Keio University
Japan
Department of Applied Chemistry, Faculty of Science  and Technology, Yokohama


Sh. Kh. Gantsev
Bashkir State Medical University; Scientific Research Institute of Oncology
Russian Federation


K. Umezawa
Aichi Medical University
Japan

Department of Molecular Target Medicine Screening, School of Medicine, Nagakute



References

1. Chen F., Wang W., EI-Deiry W. S. Current strategies to target p53 in cancer // Biochem. Pharmacol. 2010. – Vol. 80. – P. 724-730.

2. Coates J.M., Galante J.M., Bold R.J. Cancer therapy beyond apoptosis: autophagy and anoikis as mechanisms of cell death // J. Surg. Res. 2010. – Vol. 164. – P. 301-308.

3. Downward J. PI3-kinase, Akt and cell survival // Semin. Cell. Dev. Biol. 2004. – Vol. 15. – P. 177-182.

4. Govundarajan B, Sligh J.E., Vincent B.J., Li M., Canter J.A., Nickloff B.J., et al. Overexpression of Akt converts radical growth melanoma to vertical growth melanoma // J. Clin. Invest. 2007. – Vol. 117. – P. 719- 729.

5. Griswold D.P. Consideration of the subcutaneously implanted B16 melanoma as a screening model for potential anticancer agents // Cancer Chemother. Rep. 1972. – Vol. 3. – P. 315-324.

6. Grossmann J. Molecular mechanisms of detachment-induced apoptosis-anoikis // Apoptosis. 2007. – Vol. 7. – P. 247-260.

7. Ishikawa Y., Tachibana M., Matsui C., Obata R., Umezawa K., Nishiyama S. Synthesis and biological evaluation on novel analogs of 9-methyl-streptimidone, an inhibitor of NF-κB // Bioorg. Med. Chem. Lett. – 2009. – Vol. 19. – P. 1726-1728.

8. Lee C.S., Kwon Y.W., Yang H.M., Kim S.H., kim T.Y., Hur J. et al. New mechanism of rosiglitazone to reduce neointimal hyperplasia: activation of glycogen synthase kinase-3beta followed by inhibition of MMP-9. Arterioscler. Thromb // Vasc. Biol. 2009. № 29. – Р. 472-479.

9. Mendes S.S., Candi A., Vansteenbrugge M., Pignon M. R., Bult H., Boudjeltia K.Z., Munaut C., Raes M. Microarray Analyses of the Effects of NF-kappaB or PI3K Pathway Inhibitors on the LPS-induced Gene Expression Profile in RAW264.7 Cells : Synergistic Effctts of rapamycin on LPS-induced MMP9-overexpression // Cell Signal. – 2009. №21. – Р. 1109-1122.

10. Ogawara Y. Akt enhances Mdm2-mediated ubiquitination and degradation of p53 // J. Biol. Chem. 2002. – Vol. 277. – P. 21843-21850.

11. Takeiri M., Tachibana M., Kaneda A., Ito A., Ishikawa Y., Nishiyama S., Goto R., Yamashita K., Shibasaki S., Hirokata G., Ozaki M., Todo S., Umezawa K. Inhibition of macrophage activation and suppression of graft rejection by DTCM-glutarimide, a novel piperidine derived from the antibiotic 9-methylstreptimidone // Inflammation Research. 2011. – Vol. 60. – P. 879-888.

12. Vousden K.H., Lu X. Live or let die: the cell’s response to p53 // Nature Rev. Cancer. 2002. – Vol. 2. – P. 594-604.

13. Wang Z., Igarashi M., Ikeda Y., Horie R., Umezawa K. Inhibition of NF-kappa B activation by 9-methylstreptimidone isolated from Streptomyces // Heterocycles. – 2006. – Vol. 69. – P. 377-383.


Review

For citations:


Kaneda A., Gantsev Sh.Kh., Umezawa K. INHIBITION OF CELLULAR INVASION AND INDUCTION OF ANOIKIS IN MOUSE MELANOMA CELLS BY AN ANTI-INFLAMMATORY AGENT DTCM-GLUTARIMIDE. Creative surgery and oncology. 2012;(3):4-9. (In Russ.) https://doi.org/10.24060/2076-3093-2012-0-3-4-9

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ISSN 2076-3093 (Print)
ISSN 2307-0501 (Online)