Toxic effect of Polyoxometalates (POMs) with Keggin-s structure on normal and tumor cells culture

О.А. Лопатина; О.В. Бакланова; И.А. Суетина; Г.Р. Михайлова; Е.А. Гущина; Ф.В. Лисицин; Л.И. Руссу; С.А. Ковалевский; Б.А. Буданов; Ф.И. Далидчик; М.В. Мезенцева

Toxic effect of Polyoxometalates (POMs) with Keggin-s structure on normal and tumor cells culture

О.А. Лопатина¹, О.В. Бакланова², И.А. Суетина³, Г.Р. Михайлова⁴, Е.А. Гущина⁵, Ф.В. Лисицин⁶, Л.И. Руссу⁷, С.А. Ковалевский⁸, Б.А. Буданов⁹, Ф.И. Далидчик¹⁰, М.В. Мезенцева¹¹

research article Pages: 42-49

¹ к.м.н., вед. науч. со-трудник, лаборатория культур тканей, ФГБУ ФНИЦЭМ им. Н.Ф. Гамалеи Минздрава России (Москва)
² к.б.н., ст. науч. со-трудник, лаборатория культур тканей, ФГБУ ФНИЦЭМ им. Н.Ф.Гамалеи Мин-здрава России
³ к.б.н., вед. науч. со-трудник, лаборатория культур тканей, ФГБУ ФНИЦЭМ им. Н.Ф. Гамалеи Минздрава России
⁴ к.б.н., вед. науч. со-трудник, лаборатория культур тканей, ФГБУ ФНИЦЭМ им. Н.Ф.Гамалеи Мин-здрава России
⁵ к.б.н., вед. науч. сотруд-ник, лаборатория структуры и морфо-генеза вирусов, ФГБУ ФНИЦЭМ им. Н.Ф.Гамалеи Минздрава России
⁶ к.б.н., вед. науч. со-трудник, лаборатория структуры и морфогенеза вирусов, ФГБУ ФНИЦЭМ им. Н.Ф.Гамалеи Минздрава России
⁷ науч. сотрудник, лабора-тория культур тканей, ФГБУ ФНИЦЭМ им. Н.Ф.Гамалеи Минздрава России
⁸ д.ф.-м.н., лабора-тория химической физики нанострук-тур, отдел кинетики и катализа, ФГБУ Институт химической физики им. Н.Н. Семёнова РАН (Москва)
⁹ мл.науч. сотрудник, ла-боратория химической физики наност-руктур, отдел кинетики и катализа, ФГБУ Институт химической физики им. Н.Н. Семёнова РАН
¹⁰ д.ф.-м.н., профессор, лаборатория теоретических проблем химической нанофизики, отдел кинети-ки и катализа, ФГБУ Институт хими-ческой физики им. Н.Н. Семёнова РАН
¹¹ д.б.н., зав. лабораторией культур тканей, ФГБУ ФНИЦЭМ им. Н.Ф.Гамалеи Минздрава России

Keywords: cells cytotoxicity proliferative activity morphology polyoxometalates reduction potential

Abstract

Polyoxometalates (POMs) are stable metal-oxide inorganic compounds. Their structure and electronic properties can be modified. They are one of the perspective products of nanotechnology in medicine and bioengineering, in-cluding antiviral and antitumor drug development.

In this context, it is required to investigate POM-s cytotoxity on cells culture.

Objective: to investigate biological processes of different POM samples on cells culture: human embryo fibroblast (HEF), human lung embrio (HLE) and human lung carcinoma A-549.

POM cytotocxic effect on HEF cell was investigated by MTT-test.

Growth activity was measured by proliferative index and cells vitality. Cells morphology was investigated by atomic-force (AFM) and electron microscopes (EM).

Results: POM samples demonstrated various toxic effects on cells cultures. POMs (H3PW12O40, H4SiMo12O40. H3PMo12O4 ) reduced cells growth activity and led to significant morphology changes, seen in AFM and EM. Cells destruction and deterioration with failure of cytoplasm membrane structures and karyolysis, up to cells necrosis. Comparison between proliferation index and reduction potential after the 4th passage of HLE cells was realized. Correlation between proliferation index and reduction potential also was found. The most toxic samples were POM A - H3PW12O40 and POM C - H4SiW12O40. They had the lowest reduction potential. It was identified that IC50 se-quence corresponded reduction potentials. It provides the possible ways for potential medicine creation.

How to cite

Лопатина О.А., Бакланова О.В., Суетина И.А., Михайлова Г.Р., Гущина Е.А., Лисицин Ф.В., Руссу Л.И., Ковалевский С.А., Буданов Б.А., Далидчик Ф.И., Мезенцева М.В. Исследование токсического эффекта полиоксометаллатов со структурой Кеггина на культуры нормальных и онкогенных клеток // Биомедицинская радиоэлектроника. 2015. № 3. С. 42–49.

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[1] Pope M. T.Heteropoly and IsopolyOxometalates. Berlin: SpringerVerlag. 1983.

[2] Rhule J.T., Hill C.L., Judd D.A. et.al. Polyoxometalates in medicine // Chem. Rev. 1998. V.98. P.327 - 358.

[3] Shigeta S., Mori S., Yamase T. et. al. Anti-RNA virus activity of polyoxometalates // Biomed. Pharmacother. 2006. V. 60. P.211 - 219.

[4] Hosseini S.M., Amini E., Kheiri M.T. et.al. Anti-influenza Activity of a Novel Polyoxometalate Derivative (POM-4960) // Int. J. Mol. Cell. Med. Winter. 2012. V.1. № 1. P.21.

[5] Mirzojan A.F. Protivovirusnaja interferonogennaja aktivnost novogo polioksimetallata: Avtoref. kand. biol. nauk. Erevan. 2013.

[6] Yanagie H., Ogata A., Mitsui S. et al. Anticancer activity of polyoxomolybdate // Biomed. Pharmacother. 2006. V. 60. P.349 - 352.

[7] Wang Lu, Zhou Baibin, Liu Jiaren.Anticancer Polyoxometalates // Progress in Chemistry. 2013. V. 25. P. 1131 - 1141.

[8] Wang X., Liu J., Li J., Yang Y., Liu J., Li B., Pope M. T. J. Synthesis and antitumor activity of cyclopentadienyltitanium substituted polyoxotungstate [CoW₁₁₀O₃₉(CpTi)]_7t(Cp=I-O3 ₅?C₅H₅) // Inorg. Biochem. 2003. V. 94. P. 279 - 284.

[9] Ivanka Holclajtner-Antunovic and et.al. Study of some Polyoxometalates of Keggins type as potential antitumour agent // Jugoslov. MedBiochem. 2004. V. 23. P. 25 - 30.

[10] Podchernjaeva R.JA., Suetina I.A., Mikhajjlova G.R., Lopatina O.A., Bobrineckijj I.I., Morozov R.A., Seleznev A.S. Kultivirovanie perevivaemykh kletochnykh linijj na podlozhkakh iz uglerodnykh nanotrubok i vlijanie ehlektrostimuljacii na proliferaciju kletok // Voprosy virusologii. 2012. T. 57. № 5. S. 46 - 48.

[11] Suetina I.A., Podchernjaeva R.JA., Lopatina O.A., Ostroumov S.A. Toksikologija nanomaterialov: ocenki toksichnosti nanochastic okislov medi i zheleza na kulture kletok // Nanomaterialy i nanotekhnologii v zhivykh sistemakh. Bezopasnost i nanomedicina. M.: ROSNANO. 2011. S. 91.

[12] Djakonov L.D. ZHivaja kletka v kulture (metody i primenenija v biologii). M. 2009. C. 231 - 245.

[13] Jing B., Zhu Y., Hutin M., Cronin L. Polyoxometalate macroion induced phase and morphology instability of lipid membrane // Chem. Sci. 2013. V. 4. P. 3818

[14] Mori H., Mizuno N., Misono M. Factors controlling the selectivity of the oxidation of acetaldehyde over heteropoly compounds // J. Catal. 1990. V. 131. P. 133 - 142.

[15] Song I., Barteau M. Redox properties of Keggin-type heteropolyacid (HPA) catalysts: effect of counter-cation, heteroatom, and polyatom substitution // J. Molec. Catal. 2004. V. A: 212. P. 229.

[16] Yamase T., Tomita K., Sato Y., Fujita H. Antitumour and Antivirus Activities of a Curtain Polyoxometalates, Polimer in Medicine: Boimedical and Pharmaceutical Applications // Technomic Pub. Company Inc. Lancaster 1992. Chapter 13. P. 187 - 212

[17] Jurgensen A., Moffat J.B. The stability of 12-molybdosilicic, 12-tungstosilicic, 12-molybdophosphoric and 12-tungstophosphoric acids in aqueous-solution at various PH // Catal. Lett. 1995. V. 34. P. 237.

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