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Salnikova, Diana, Krymov, Stepan, Bogdanov, Fedor, Sorokin, Danila, Andreeva, Olga, Khamidullina, Alvina, Shchekotikhin, Andrey, Scherbakov, Alexander. (1404). Research on the synergistic effect of a novel apoptosis inducer combined with AKT and HSP90 selective inhibitors on hormone-sensitive and hormone-resistant breast cancer cell lines. سامانه مدیریت نشریات علمی, 80(3), 791-800. doi: 10.32592/ARI.2025.80.3.791
Diana I. Salnikova; Stepan K. Krymov; Fedor B. Bogdanov; Danila V. Sorokin; Olga E. Andreeva; Alvina I. Khamidullina; Andrey E. Shchekotikhin; Alexander M. Scherbakov. "Research on the synergistic effect of a novel apoptosis inducer combined with AKT and HSP90 selective inhibitors on hormone-sensitive and hormone-resistant breast cancer cell lines". سامانه مدیریت نشریات علمی, 80, 3, 1404, 791-800. doi: 10.32592/ARI.2025.80.3.791
Salnikova, Diana, Krymov, Stepan, Bogdanov, Fedor, Sorokin, Danila, Andreeva, Olga, Khamidullina, Alvina, Shchekotikhin, Andrey, Scherbakov, Alexander. (1404). 'Research on the synergistic effect of a novel apoptosis inducer combined with AKT and HSP90 selective inhibitors on hormone-sensitive and hormone-resistant breast cancer cell lines', سامانه مدیریت نشریات علمی, 80(3), pp. 791-800. doi: 10.32592/ARI.2025.80.3.791
Salnikova, Diana, Krymov, Stepan, Bogdanov, Fedor, Sorokin, Danila, Andreeva, Olga, Khamidullina, Alvina, Shchekotikhin, Andrey, Scherbakov, Alexander. Research on the synergistic effect of a novel apoptosis inducer combined with AKT and HSP90 selective inhibitors on hormone-sensitive and hormone-resistant breast cancer cell lines. سامانه مدیریت نشریات علمی, 1404; 80(3): 791-800. doi: 10.32592/ARI.2025.80.3.791

Research on the synergistic effect of a novel apoptosis inducer combined with AKT and HSP90 selective inhibitors on hormone-sensitive and hormone-resistant breast cancer cell lines

Archives of Razi Institute
مقاله 29، دوره 80، شماره 3، مرداد و شهریور 2025، صفحه 791-800    اصل مقاله (489.71 K)
نوع مقاله: Short Communication
شناسه دیجیتال (DOI): 10.32592/ARI.2025.80.3.791
نویسندگان
Diana I. Salnikova* 1؛ Stepan K. Krymov2؛ Fedor B. Bogdanov3؛ Danila V. Sorokin1؛ Olga E. Andreeva1؛ Alvina I. Khamidullina4؛ Andrey E. Shchekotikhin2؛ Alexander M. Scherbakov1
1Department of Experimental Tumor Biology, Blokhin N.N. National Medical Research Center of Oncology, Kashirskoe shosse 24, Moscow 115522, Russia
2Gause Institute of New Antibiotics, Bol’shaya Pirogovskaya street 11, Moscow 119021, Russia
3Department of Experimental Tumor Biology, Blokhin N.N. National Medical Research Center of Oncology, Kashirskoe shosse 24, Moscow 115522, Russia; Faculty of Medicine, Moscow State University, Lomonosovsky prospect 27 bldg. 1, Moscow 119991, Russia
4Laboratory of Molecular Oncobiology, Institute of Gene Biology Russian Academy of Sciences, Vavilova Street 34/5, Moscow 119334, Russia
چکیده
One of the frequent malignant tumors affecting women is breast cancer. This tumor develops and occurs due to several internal and external factors. Resistance is a key challenge in modern breast cancer therapy. Novel 1-substituted isatin-5-sulfonamides with antiproliferative effects on the basis of isatin-core-contained antitumor compounds were synthesized in three stages via alkylation with benzyl chlorides. The work aims at the synergistic effect of the obtained 1-substituted isatin-5-sulfonamides exhibiting pro-apoptotic activity and combined with heat shock protein 90 (HSP90) and protein kinase B (AKT) selective inhibitors in breast cancer cell lines, which are sensitive and resistant to antiestrogens. 4-hydroxytamoxifen (HT) was applied to create a resistant cell subline (MCF7/HT); a resistance index amounted to 2. MCF7/p53-LUC cell subline was obtained through transfection using the p53-responsive luciferase reporter plasmid. Lead compound LCTA-3344 exhibited the most significant antiproliferative effect; its half-maximal inhibitory concentration (IC50) on MCF7/HT (1.4±0.1 μМ) was less compared to that on MCF7 (2.6±0.3 μМ). Combinations of apoptosis inducer LCTA-3344 and AKT Inhibitor IV were synergistic on MCF7 and MCF7/HT, demonstrating the combination index (CI) values of 0.8 and 0.4 (a higher activity), respectively. Apoptosis inducer LCTA-3344 combined with AKT Inhibitor X and HSP90 inhibitor did not show such significant activity with a minimal CI value of 0.9. Compound LCTA-3344 did not enhance luciferase activity in MCF7/p53-LUC cell subline, while chemotherapeutic agent doxorubicin has been determined to be its potent inducer. In conclusion, apoptosis inducer LCTA-3344 was 1.9-fold more active toward MCF7/HT in comparison to the parental cell line. Compound LCTA-3344 together with AKT Inhibitor IV was the most active drug combination on the MCF7/HT subline, with a CI of 0.4. Compound LCTA-3344 induced apoptosis through a p53-independent mechanism, which holds promise as a novel therapy for hormone-resistant breast cancers. AKT Inhibitor IV caused apoptosis of MCF7 cells to a greater extent than compound LCTA-3344, and their combination resulted in a synergistic effect.
کلیدواژه‌ها
MCF7 breast cancer cell line؛ AKT Inhibitor IV؛ Isatin-5-sulfonamides؛ Synergism؛ Resistance
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