Cytotoxicity of SHIP2 Silencing in MDA-MB-231 Breast Cancer Cell Line
DOI:
https://doi.org/10.32947/ajps.v25i5.1332Keywords:
SHIP2 silencing, Apoptosis, MDA-231 breast cancer cell lineAbstract
Background: Breast cancer is a serious global health risk to women. Compared to other forms of BC. Triple negative breast cancer is characterized by a poor prognosis, high levels of aggressiveness and proliferation, and rapid progression. The phosphoinositide 3-kinase/ protein kinase B/ mechanistic target of rapamycin signaling pathway is commonly over-activated in human cancers and plays a role in BC survival, proliferation and angiogenesis. The SH2-containing 5´ inositol phosphatases 1 and 2, contribute to the regulation of the phosphoinositide 3-kinase/ protein kinase B signaling pathway that has a role in progression of cancer.
Objective: To address the cytotoxic effect of SH2-containing 5´ inositol phosphatases 2 silencing in MDA-MB-231 BC cell line.
Methods: The MDA-MB-231 cells were cultured in Dulbecco’s modified Eagle’s medium with low glucose, with and without SHIP2- small interfering ribonucleic acid for SH2-containing 5´ inositol phosphatases 2 transfection. The cytotoxicity of SH2-containing 5´ inositol phosphatases 2 silencing was assessed by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Apoptosis was assessed using Annexin V-fluorescein isothiocyanate/ propidium iodide staining.
Results: Transfection of MDA-MB-231 BC cells with (0.04 µM) of SHIP2-siRNA significantly reduced cell viability at 24 hours post-transfection, and significantly induced apoptosis compared to control untreated cells. Conclusion: The present study provided evidence that SHIP2-siRNA reduced viability and induced apoptosis at 24 hours post-transfection in MDA-MB-231 BC cells.
References
1. Ge A, He Q, Zhao D, Li Y, Chen J, Deng Y, et al. Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis. Journal of cellular and molecular medicine. 2024;28(1):e18044.
2. Al-Saigh TH, Al-bayati SA, Abdul-mawjood SA, Ahmed FA. Breast Cancer in Mosul: A Survival Analysis. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2020;20(2):31-6.
3. Bedewi BK, Jasim GA, Abbas IS, Al-Sudani B. Cytotoxicity of Cryptochlorogenic acid against Breast cancer cell line (MCF7) isolated from Moringa oleifera Leaves Cultivated in Iraq. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2022;22(2):35-43.
4. Salih AI, Al-Sudani BT, Mshimesh BA-R. Targeting POLD1 to suppress the proliferation and migration of breast cancer MDA-MB-231 cell lines by downregulation of SIRT1. Toxicology Research. 2024;13(4):tfae111.
5. Vagia E, Mahalingam D, Cristofanilli MJC. The landscape of targeted therapies in TNBC. Cancers. 2020;12(4):916.
6. Zhang J, Zhou K, Lin J, Yao X, Ju D, Zeng X, et al. Ferroptosis-enhanced chemotherapy for triple-negative breast cancer with magnetic composite nanoparticles. Biomaterials. 2023;303:122395.
7. Zhang H-p, Jiang R-y, Zhu J-y, Sun K-n, Huang Y, Zhou H-h, et al. PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer. Breast Cancer. 2024;31(4):539-51.
8. Pedicone C, Meyer ST, Chisholm JD, Kerr WGJC. Targeting SHIP1 and SHIP2 in Cancer. Cancers. 2021;13(4):890.
9. Ghosh S, Scozzaro S, Ramos AR, Delcambre S, Chevalier C, Krejci P, et al. Inhibition of SHIP2 activity inhibits cell migration and could prevent metastasis in breast cancer cells. Journal of cell science. 2018;131(16).
10. Salih AI, Mshimesh BA-R, Al-Sudani BTA-RJoMS. Investigating the Effect of EX-527 as SIRT1 Inhibitor in Breast Cancer Cell Line. Al-Rafidain Journal of Medical Sciences. 2024;7(1 (Special)):S64-9.
11. Al-khfajy WS, Arif IS, Al-sudani BT. Synergistic effect of obeticholic acid and fasting-mimicking on proliferative, migration, and survival signaling in prostate cancer. Pharmacia. 2022;69:579-87.
12. Luo SX, Liu JE, Cheng ASK, Xiao SQ, Su YL, Feuerstein M. Breast Cancer Survivors Report Similar Concerns Related to Return to Work in Developed and Developing Nations. Journal of occupational rehabilitation. 2019;29(1):42-51.
13. Li J, He D, Li S, Xiao J, Zhu Z. Ferroptosis: the emerging player in remodeling triple-negative breast cancer. Frontiers in immunology. 2023;14:1284057.
14. Ye Y, Ge YM, Xiao MM, Guo LM, Li Q, Hao JQ, et al. Suppression of SHIP2 contributes to tumorigenesis and proliferation of gastric cancer cells via activation of Akt. Journal of gastroenterology. 2016;51(3):230-40.
15. Fuhler GM, Brooks R, Toms B, Iyer S, Gengo EA, Park M-Y, et al. Therapeutic potential of SH2 domain-containing inositol-5′-phosphatase 1 (SHIP1) and SHIP2 inhibition in cancer. Molecular medicine. 2012;18:65-75.
16. Tang T, Xiao Z-Y, Shan G, Lei H-B. Descending-SHIP2-mediated radiosensitivity enhancement through PI3K/Akt signaling pathway in laryngeal squamous cell carcinoma. Biomedicine & Pharmacotherapy. 2019;118:109392.
17. Müller SM, Jücker M. The Functional Roles of the Src Homology 2 Domain-Containing Inositol 5-Phosphatases SHIP1 and SHIP2 in the Pathogenesis of Human Diseases. International journal of molecular sciences. 2024;25(10).
18. Zhou J, Di M, Han H, therapy. Upregulation of SHIP2 participates in the development of breast cancer via promoting Wnt/β-catenin signaling. OncoTargets. 2019:7067-77.
19. Wu H, Li X, Feng M, Yao L, Deng Z, Zao G, et al. Downregulation of RNF138 inhibits cellular proliferation, migration, invasion and EMT in glioma cells via suppression of the Erk signaling pathway. Oncology reports. 2018;40(6):3285-96.
20. Liu RT, Cao JL, Yan CQ, Wang Y, An CJ, Lv HT. Effects of LncRNA-HOST2 on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma cell line SMMC-7721. Bioscience reports. 2017;37(2).
21. Wang Z, Li R, He Y, Huang S. Effects of secreted frizzled-related protein 1 on proliferation, migration, invasion, and apoptosis of colorectal cancer cells. Cancer cell international. 2018;18:48.
22. Ghosh S, Scozzaro S, Ramos AR, Delcambre S, Chevalier C, Krejci P, et al. Inhibition of SHIP2 activity inhibits cell migration and could prevent metastasis in breast cancer cells. Journal of cell science. 2018;131(16):jcs216408.
23. Tang T, Xiao Z-Y, Shan G, Lei H-B. Descending-SHIP2-mediated radiosensitivity enhancement through PI3K/Akt signaling pathway in laryngeal squamous cell carcinoma. Biomedicine & Pharmacotherapy 2019;118:109392.
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Copyright (c) 2025 Rua Abbas Naser, Inam Sameh Arif, Basma Talib Al-Sudani, Sayed Mahmood Alqallaf
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