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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 (489.83 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
مراجع
  1. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019;394(10204):1159-68.
  2. Wang J, Wu SG. Breast Cancer: An Overview of Current Therapeutic Strategies, Challenge, and Perspectives. Breast cancer (Dove Medical Press). 2023;15:721-30.
  3. Hameed BH, Abdulsatar Al-Rayahi I, Muhsin SS. The Preoperative Serum Levels of the Anaphylatoxins C3a and C5a and Their Association with Clinico-Pathological Factors in Breast Cancer Patients. Archives of Razi Institute. 2022;77(5):1873-9.
  4. Onkar SS, Carleton, N. M., Lucas, P. C., Bruno, T. C., Lee, A. V., Vignali, D. A. A., Oesterreich, S. The Great Immune Escape: Understanding the Divergent Immune Response in Breast Cancer Subtypes. Cancer Discov. 2023;13(1):23-40.
  5. Sorokin DV, Krymov SK, Cherednichenko MN, Mikhaylova AL, Salnikova DI, Shchekotikhin AE, et al. Inhibitory Effects of 5-Fluorouracil on the Growth of 4-Hydroxytamoxifen-Resistant and Sensitive Breast Cancer Cells. Engineering Proceedings. 2023;56(1):192.
  6. Al-Thoubaity FK. Molecular classification of breast cancer: A retrospective cohort study. Annals of medicine and surgery (2012). 2020;49:44-8.
  7. Scherbakov AM, Krasil'nikov MA, Kushlinskii NE. Molecular mechanisms of hormone resistance of breast cancer. Bulletin of experimental biology and medicine. 2013;155(3):384-95.
  8. Mohammed Alwan A, Tavakol Afshari J, Afzaljavan F. Significance of the Estrogen Hormone and Single Nucleotide Polymorphisms in the Progression of Breast Cancer among Female. Archives of Razi Institute. 2022;77(3):943-58.
  9. Lee JJ-K, Jung, Y. L., Cheong, T.-C., Valle-Inclan, J. E., Chu, C., Gulhan, D. C., Ljungström, V., Jin, H., Viswanadham, V. V., Watson, E. V., Cortés-Ciriano, I., Elledge, S. J., Chiarle, R., Pellman, D., Park, P. J. ERα-associated translocations underlie oncogene amplifications in breast cancer. Nature. 2023;618(7967):1024-32.
  10. Bogush TA, Polezhaev BB, Mamichev IA, Bogush EA, Polotsky BE, Tjulandin SA, et al. Tamoxifen Never Ceases to Amaze: New Findings on Non-Estrogen Receptor Molecular Targets and Mediated Effects. Cancer Invest. 2018;36(4):211-20.
  11. Jordan VC. 50th anniversary of the first clinical trial with ICI 46,474 (tamoxifen): then what happened? Endocrine-related cancer. 2021;28(1):R11-r30.
  12. Ebright RY, Lee, S., Wittner, B. S., Niederhoffer, K. L., Nicholson, B. T., Bardia, A., Truesdell, S., Wiley, D. F., Wesley, B., Li, S., Mai, A., Aceto, N., Vincent-Jordan, N., Szabolcs, A., Chirn, B., Kreuzer, J., Comaills, V., Kalinich, M., Haas, W., Ting, D. T., Toner, M., Vasudevan, S., Haber, D. A., Maheswaran, S., Micalizzi, D. S. Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis. Science. 2020;367(6485):1468-73.
  13. Ma Y, Vassetzky, Y., Dokudovskaya, S. mTORC1 pathway in DNA damage response. Biochim Biophys Acta Mol Cell Res. 2018;1865(9):1293-311.
  14. Nitulescu GM, Van De Venter M, Nitulescu G, Ungurianu A, Juzenas P, Peng Q, et al. The Akt pathway in oncology therapy and beyond (Review). International journal of oncology. 2018;53(6):2319-31.
  15. Mundi PS, Sachdev J, McCourt C, Kalinsky K. AKT in cancer: new molecular insights and advances in drug development. British journal of clinical pharmacology. 2016;82(4):943-56.
  16. Cole PA, Chu N, Salguero AL, Bae H. AKTivation mechanisms. Current opinion in structural biology. 2019;59:47-53.
  17. Scherbakov AM, Bogdanov, F. B., Mikhaylova, A. L., Andreeva, O. E., Salnikova, D. I. Targeting AKT Kinase in Hydroxytamoxifen-Resistant Breast Cancer Cells. Med Sci Forum. 2023;20(1):4.
  18. Rochani AК, Balasubramanian, S., Girija, A. R., Maekawa, T., Kaushal, G., Kumar, D. S. Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation for Cancer Therapy. Polymers. 2020;12(8).
  19. Shomali M, Cheng, J., Sun, F., Koundinya, M., Guo, Z., Hebert, A. T., McManus, J., Levit, M. N., Hoffmann, D., Courjaud, A., Arrebola, R., Cao, H., Pollard, J., Lee, J. S., Besret, L., Caron, A., Bangari, D. S., Abecassis, P.-Y., Schio, L., El-Ahmad, Y., Halley, F., Tabart, M., Certal, V., Thompson, F., McCort, G., Filoche-Rommé, B., Cheng, H., Garcia-Echeverria, C., Debussche, L., Bouaboula, M. SAR439859, a Novel Selective Estrogen Receptor Degrader (SERD), Demonstrates Effective and Broad Antitumor Activity in Wild-Type and Mutant ER-Positive Breast Cancer Models. Mol Cancer Ther. 2021;20(2):250-62.
  20. Saatci O, Huynh-Dam, K.-T., Sahin, O. Endocrine resistance in breast cancer: from molecular mechanisms to therapeutic strategies. J Mol Med (Berl). 2021;99(12):1691-710.
  21. Hopcroft L, Wigmore, E. M., Williamson, S. C., Ros, S., Eberlein, C., Moss, J. I., Urosevic, J., Carnevalli, L. S., Talbot, S., Bradshaw, L., Blaker, C., Gunda, S., Owenson, V., Hoffmann, S., Sutton, D., Jones, S., Goodwin, R. J. A., Willis, B. S., Rooney, C., de Bruin, E. C., Barry, S. T. Combining the AKT inhibitor capivasertib and SERD fulvestrant is effective in palbociclib-resistant ER+ breast cancer preclinical models. NPJ Breast Cancer. 2023;9(1):64.
  22. Krymov SK, Scherbakov AM, Dezhenkova LG, Salnikova DI, Solov'eva SE, Sorokin DV, et al. Indoline-5-Sulfonamides: A Role of the Core in Inhibition of Cancer-Related Carbonic Anhydrases, Antiproliferative Activity and Circumventing of Multidrug Resistance. Pharmaceuticals (Basel, Switzerland). 2022;15(12).
  23. Krymov SK, Salnikova DI, Dezhenkova LG, Bogdanov FB, Korlyukov AA, Scherbakov AM, et al. Synthesis and Biological Evaluation of Chalconesulfonamides: En Route to Proapoptotic Agents with Antiestrogenic Potency. Pharmaceuticals (Basel, Switzerland). 2023;17(1).
  24. Krymov SK, Scherbakov, A. M., Salnikova, D. I., Sorokin, D. V., Dezhenkova, L. G., Ivanov, I. V., Vullo, D., De Luca, V., Capasso, C., Supuran, C. T., Shchekotikhin, A. E. Synthesis, biological evaluation, and in silico studies of potential activators of apoptosis and carbonic anhydrase inhibitors on isatin-5-sulfonamide scaffold. Eur J Med Chem. 2022;228:113997.
  25. Salnikova DI, Krymov SK, Sorokin DV, Bogdanov FB, Andreeva OE, Khamidullina AI, et al. Development of Synergetic Combinations of a Novel Apoptosis Inducer with AKT and Hsp90 Selective Inhibitors Targeting Hormone-Sensitive and Hormone-Resistant Breast Cancer Cells. Proceedings. 2024;100(1):4.
  26. Sorokin DV, Krymov, S. K., Cherednichenko, M. N., Mikhaylova, A. L., Salnikova, D. I., Shchekotikhin, A. E., Scherbakov, A. M. Inhibitory Effects of 5-Fluorouracil on the Growth of 4-Hydroxytamoxifen-Resistant and Sensitive Breast Cancer Cells. Engineering Proceedings. 2023;56(1):192.
  27. Ilovaisky AI, Merkulova, V. M., Chernoburova, E. I., Shchetinina, M. A., Salnikova, D. I., Scherbakov, A. M., Zavarzin, I. V., Terent'ev, A. O. Secosteroidal hydrazides: Promising scaffolds for anti-breast cancer agents. J Steroid Biochem Mol Biol. 2021;214:106000.
  28. Chou T-C. Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method. Cancer Res. 2010;70(2):440–6.
  29. Scherbakov AM, Borunov AM, Buravchenko GI, Andreeva OE, Kudryavtsev IA, Dezhenkova LG, et al. Novel Quinoxaline-2-Carbonitrile-1,4-Dioxide Derivatives Suppress HIF1α Activity and Circumvent MDR in Cancer Cells. Cancer Investigation. 2018;36(3):199-209.
  30. Scherbakov AM, Komkov AV, Komendantova AS, Yastrebova MA, Andreeva OE, Shirinian VZ, et al. Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells. Frontiers in pharmacology. 2017;8:979.
  31. Zapevalova MV, Shchegravina, E. S., Fonareva, I. P, Salnikova, D. I., Sorokin, D. V., Scherbakov, A. M., Maleev, A. A., Ignatov, S. K., Grishin, I. D., Kuimov, A. N., Konovalova, M. V., Svirshchevskaya, E. V., Fedorov, A. Y. Synthesis, Molecular Docking, In Vitro and In Vivo Studies of Novel Dimorpholinoquinazoline-Based Potential Inhibitors of PI3K/Akt/mTOR Pathway. Int J Mol Sci. 2022;23(18):10854.
  32. Mruk DD, Cheng CY. Enhanced chemiluminescence (ECL) for routine immunoblotting: An inexpensive alternative to commercially available kits. Spermatogenesis. 2011;1(2):121-2.
  33. Nicolini A, Ferrari, P., Kotlarova, L., Rossi, G., Biava, P. M. The PI3K-AKt-mTOR Pathway and New Tools to Prevent Acquired Hormone Resistance in Breast Cancer. Curr Pharm Biotechnol. 2015;16(9):804-15.
  34. Quirke VM. Tamoxifen from Failed Contraceptive Pill to Best-Selling Breast Cancer Medicine: A Case-Study in Pharmaceutical Innovation. Frontiers in pharmacology. 2017;8:620.
  35. Chang M. Tamoxifen resistance in breast cancer. Biomolecules & therapeutics. 2012;20(3):256-67.
  36. Ichikawa K, Ito, S., Kato, E., Abe, N., Machida, T., Iwasaki, J., Tanaka, G., Araki, H., Wakayama, К., Jona, H., Sugimoto, T., Miyadera, К., Ohkubo, S. TAS0612, a novel RSK, AKT, and S6K inhibitor, exhibits antitumor effects in preclinical tumor models. Mol Cancer Ther. 2023;10.1158/1535-7163.MCT-21-1037.
  37. Cocco S, Leone, A., Roca, M. S., Lombardi, R., Piezzo, M., Caputo, R., Ciardiello, C., Costantini, S., Bruzzese, F., Sisalli, M. J., Budillon, A., De Laurentiis, M. Inhibition of autophagy by chloroquine prevents resistance to PI3K/AKT inhibitors and potentiates their antitumor effect in combination with paclitaxel in triple negative breast cancer models. J Transl Med. 2022;20(1):290.
  38. Balasis ME, Forinash, К. D., Chen, Y. A., Fulp, W. J., Coppola, D., Hamilton, A. D., Cheng, J. Q., Sebti, S. M. Combination of farnesyltransferase and Akt inhibitors is synergistic in breast cancer cells and causes significant breast tumor regression in ErbB2 transgenic mice. Clin Cancer Res. 2011;17(9):2852-62.
  39. Tian X, Wu, L., Jiang, M., Zhang, Z., Wu, R., Miao, J., Liu, C., Gao, S. Downregulation of GLYAT Facilitates Tumor Growth and Metastasis and Poor Clinical Outcomes Through the PI3K/AKT/Snail Pathway in Human Breast Cancer. Front Oncol. 2021;11:641399.
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تعداد مشاهده مقاله: 262
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