Rhodospirillum rubruml-asparaginase targets tumor growth by a dual mechanism involving telomerase inhibition
| Autor: | Olga V. Podobed, Dmitry D. Zhdanov, Marsel M. Basharov, Mikhail A. Eldarov, D. V. Grishin, Vadim S. Pokrovsky, Svetlana S. Alexandrova, Sokolov Nn, Yulia A. Gladilina, M. V. Pokrovskaya |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Asparaginase Telomerase Biophysics Down-Regulation Mice Nude Antineoplastic Agents Biology Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Neoplasms Animals Humans Point Mutation Telomerase reverse transcriptase Enzyme Inhibitors Molecular Biology Rhodospirillum Telomere Shortening Mice Inbred BALB C Cell Biology Molecular biology Telomere 030104 developmental biology Real-time polymerase chain reaction chemistry Cell culture 030220 oncology & carcinogenesis Cancer cell Female |
| Zdroj: | Biochemical and biophysical research communications. 492(2) |
| ISSN: | 1090-2104 |
| Popis: | Rhodospirillum rubrum l -asparaginase mutant RrA E149R, V150P, F151T (RrA) was previously identified to down-regulate telomerase activity along with catalyzing the hydrolysis of l -asparagine. The aim of this study was to define the effect of prolonged RrA exposure on telomerase activity, maintenance of telomeres and proliferation of cancer cells in vitro and in vivo . RrA could inhibit telomerase activity in SCOV-3, SkBr-3 and A549 human cancer cell lines due to its ability to down-regulate the expression of telomerase catalytic subunit hTERT. Telomerase activity in treated cells did not exceeded 29.63 ± 12.3% of control cells. Continuous RrA exposure of these cells resulted in shortening of telomeres followed by cell death in vitro . Using real time PCR we showed that length of telomeres in SCOV-3 cells has been gradually decreasing from 10105 ± 2530 b.p. to 1233 ± 636 b.p. after 35 days of cultivation. RrA treatment of xenograft models in vivo showed slight inhibition of tumor growth accompanied with 49.5–53.3% of decrease in hTERT expression in the all tumors. However down-regulation of hTERT expression, inhibition of telomerase activity and the loss of telomeres was significant in response to RrA administration in xenograft models. These results should facilitate further investigations of RrA as a potent therapeutic protein. |
| Databáze: | OpenAIRE |
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