Antitumor efficiency of fascaplysin synthetic derivatives (7-phenylfascaplysin, 3-chlorofascaplysin, 3-bromofascaplysin, and 10-bromofascaplysin) was compared out in vitro on C6 glioma cells. The cytotoxic efficiency of all tested compounds was higher than that of unsubstituted fascaplysin; 3-bromofascaplysin and 7-phenylfascaplysin exhibited the best capacity to kill glioma C6 cells. Apoptosis was the main mechanism of glioma cell death. The cytotoxic activity of these compounds increased with prolongation of exposure to the substance and increase of its concentration. Fascaplysin derivatives modified all phases of glioma cell vital cycle. The count of viable tumor cell in G0 phase remained minimum by the end of experiment under the effects of 3-bromofascaplysin and 7-phenylfascaplysin.
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Bharate SB, Manda S, Mupparapu N, Battini N, Vishwakarma RA. Chemistry and biology of fascaplysin a potent marine derived CDK-4 inhibitor. Mini Rev. Med. Chem. 2012;12(7):650-664.
Hörmann A, Chaudhuri B, Fretz H. DNA Binding Properties of the Marine Sponge Pigment Fascaplysin. Bioorg. Med. Chem. 2001;9(4):917-921.
Kumar S, Guru SK, Pathania AS, Manda S, Kumar A, Bharate SB, Vishwakarma RA, Malik F, Bhushan S. Fascaplysin induces caspase mediated crosstalk between apoptosis and autophagy through the inhibition of PI3K/AKT/mTOR signaling cascade in human leukemia HL-60 cells. J. Cell. Biochem. 2015;116(6):985-997.
Kuzmich AS, Fedorov SN, Shastina VV, Shubina LK, Radchenko OS, Balaneva NN, Zhidkov ME, Park JI, Kwak JY, Stonik VA. The anticancer activity of 3- and 10-bromofascaplysins is mediated by caspase-8, -9, -3-dependent apoptosis. Bioorg. Med. Chem. 2010;18(11):3834-3840.
Omuro A, DeAngelis LM. Glioblastoma and others malignant gliomas: a clinical review. JAMA. 2013;310(17):1842-1850.
Segraves NL, Robinson SJ, Garcia D, Said SA, Fu X, Schmitz FJ, Pietraszkiewicz H, Valeriote FA, Crews P. Crews comparison of fascaplysin and related alkaloids: a study of structures, cytotoxicities, and sources. J. Nat. Prod. 2004;67(5):783-792.
Soni R, Muller L, Furet P, Schoepfer J, Stephan C, Zumstein-Mecker S, Fretz H, Chaudhuri B. Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product. Biochem. Biophys. Res. Commun. 2000;275(3):877-884.
Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. 2015;314(23):2535-2543.
Valeriote FA, Tenney K, Media J, Pietraszkiewicz H, Edelstein M, Johnson TA, Amagata T, Crews P. Discovery and development of anticancer agents from marine sponges: perspectives based on a chemistry-experimental therapeutics collaborative program. J. Exp. Ther. Oncol. 2012;10(2):119-134.
Zheng YL, Lu XL, Lin J, Chen HM, Yan XJ, Wang F, Xu WF. Direct effects of fascaplysin on human umbilical vein endothelial cells attributing the anti-angiogenesis activity. Biomed. Pharmacother. 2010;64(8):527-533.
Zhidkov ME, Baranova OV, Dubovitskii SV, Balaneva NN, Fedorov SN, Radchenko OS. The first syntheses of 3-bromofascaplysin, 10-bromofascaplysin and 3,10-dibromofascaplysin-marine alkaloids from Fascaplysinopsis reticulata and Didemnum sp. by application of a simple and effective approach to the pyrido[1,2-a:3,4-b’]diindole system. Tetrahedron Lett. 2007;48(5):7998-8000.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 164, No. 11, pp. 622-629, November, 2017
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Lyakhova, I.A., Bryukhovetsky, I.S., Kudryavtsev, I.V. et al. Antitumor Activity of Fascaplysin Derivatives on Glioblastoma Model In Vitro. Bull Exp Biol Med 164, 666–672 (2018). https://doi.org/10.1007/s10517-018-4055-4
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DOI: https://doi.org/10.1007/s10517-018-4055-4