Benzimidazolün Fare 4T1 Hücre Kültüründeki Apoptoz Aktivasyonunun ve Sitotoksisitesinin MTT Hücre Canlılık Testi ve İmmunsitokimya Yöntemleriyle Araştırılması
Abstract
Kanser, küresel olarak önemli bir sağlık sorunu olarak bilinmektedir. Meme kanseri en yaygın kötü huylu tümördür ve metastaz kötü prognozun başlıca nedeni olmaya devam etmektedir. Son yıllarda kanser tedavisindeki gelişmelere rağmen, metastatik meme kanseri tedavisinin başarısı istenen düzeyde değildir. Son yıllarda keşfedilen antikanser ilaçları arasında, çeşitli biyolojik aktiviteleri ve klinik uygulamaları nedeniyle çeşitli benzimidazol türevleri antikanser ajanı geliştirmede dikkat çekmiştir. Bu çalışmanın amacı, 4T1 meme kanseri hücre hattında, sentezlenen benzimidazol türevi olan SA-61’in antiproliferatif aktivitesini, FDA tarafından meme kanseri tedavisi için onaylanan abemaciclib ile karşılaştırmalı olarak değerlendirmektir. SA-61’in antiproliferatif aktivitesi ve apoptotik etkisi sırasıyla MTT ve imunohistokimyasal yöntemler kullanılarak incelendi. MTT sonuçlarına göre SA-61 bileşiği 4T1 hücrelerinde doza bağlı bir şekilde antiproliferatif aktivite gösterdi fakat bu etki abemaciclibe kıyasla daha düşüktür. Kanser karşıtı aktivitesinde rol oynayan bileşiklerin spesifik olarak belirlenmesi için daha fazla çalışmaya ihtiyaç duyulmasına rağmen, bulgularımız SA-61’in 4T1 hücrelerinin çoğalmasını engellediğini ve etkisinin doza bağlı olduğunu göstermektedir.
References
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Using the MTT Cell Viability Test and Immunocytochemistry Techniques, Benzimidazole's Cytotoxicity and Apoptosis Activation in Mouse 4T1 Cell Culture
Abstract
Cancer is known as a major health problem globally. Breast cancer is the most common malignant tumor and metastasis continues to be the main cause of poor prognosis. Despite recent advances in cancer treatment, the success of metastatic breast cancer treatment is not at the desired level. Among the anticancer drugs discovered in recent years, various benzimidazole derivatives have attracted attention in the development of anticancer agents due to their various biological activities and clinical applications. The aim of this study was to evaluate the antiproliferative activity of synthesized benzimidazole derivative SA-61 in 4T1 breast cancer cell line in comparison with abemaciclib, which is approved by FDA for the treatment of breast cancer. The antiproliferative activity and apoptotic effect of SA-61 were examined using MTT and immunohistochemical methods, respectively. According to MTT results, compound SA-61 showed antiproliferative activity in 4T1 cells in a dose-dependent manner, but this effect was lower than abemaciclib. Although further studies are needed to specifically identify the compounds involved in its anti-cancer activity, our findings suggest that SA-61 inhibits the proliferation of 4T1 cells and its effect is dose dependent.
References
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- Medeiros B, Allan AL (2019). Molecular mechanisms of breast cancer metastasis to the lung: clinical and experimental perspectives. Int. J. Mol. Sci. 20:2272.
- Pulaski BA, Ostrand-Rosenberg S (2001). Mouse 4T1 breast tumor model. Curr. Protoc Immunol. 39:20.2.1–20.2.16.
- Wagenblast E, Soto M, Gutiérrez-Ángel S, et al. (2015). A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis. Nature. 520:358–362.
- Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L (2016). Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 13:674–690.
- Lee YT, Tan YJ, Oon CE (2023). Benzimidazole and its derivatives as cancer therapeutics: The potential role from traditional to precision medicine. Acta Pharm Sin B. 13(2):478-497.
- Hagar FF, Abbas SH, Atef E, Abdelhamid D, Abdel-Aziz M (2025). Benzimidazole scaffold as a potent anticancer agent with different mechanisms of action (2016-2023). Mol Divers. 29(2):1821-1849.
- Liu Y (2021). Abemaciclib sensitizes HPV-negative cervical cancer to chemotherapy via specifically suppressing CDK4/6-Rb-E2F and mTOR pathways. Fundam Clin Pharmacol. 35(1):156–64.
- Schettini F (2018). CDK 4/6 inhibitors as single agent in advanced solid tumors. Front Oncol. 8:608.
- Akkoç S, Gök Y, İlhan İÖ, Kayser V (2016). N-Methylphthalimide-substituted benzimidazolium salts and PEPPSI Pd–NHC complexes: synthesis, characterization and catalytic activity in carbon–carbon bond-forming reactions. Beilstein J. Org. Chem. 12, 81–88.
- Bilici E, Akkoç S (2025). Investigation of the cytotoxic effect of a new n-phenyl benzimidazole derivative on cell viability in A549 and HepG2 cell lines. Van Med J, 32(1), 3-6.
- Mavvaji M, Zeyrek CT, Akkoc S (2024). Investigation of the cytotoxic activity, DFT calculation, and docking studies newly synthesized 1,3-disubstituted benzimidazolium chlorides on human liver cancer, lung cancer, and normal embryonic kidney cell lines. Biochem Biophys Res Commun. 741:151024.
- Siegel RL, Miller KD, Wagle NS, et al. (2023). Cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 73(1):17–48.
- Xia CF, Dong XS, Li H, et al. (2022). Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chinese Medical Journal. 135(5):584–590.
- Park M, Kim D, Ko S, et al. (2022). Breast cancer metastasis: mechanisms and therapeutic implications. Int J Mol Sci., 23(12):6806.
- Waks AG. Winer EP (2019). Breast cancer treatment: a review. JAMA, 321, 288–300.
- Alian DME, Helmy MW, Haroun M, Moussa N (2024). Modulation of autophagy and apoptosis can contribute to the anticancer effect of Abemaciclib/Celecoxib combination in colon cancer cells. Med Oncol. 3;41(2):43.
- Hino H (2020). Abemaciclib induces atypical cell death in cancer cells characterized by formation of cytoplasmic vacuoles derived from lysosomes. Cancer Sci. 111(6):2132–45.
- Sadasivan S (2006). Amino acid Starvation induced autophagic cell death in PC-12 cells: evidence for activation of caspase-3 but not calpain-1. Apoptosis. 11(9):1573–82
- Sirois I (2012). Caspase activation regulates the extracellular export of autophagic vacuoles. Autophagy. 8(6):927–37.
- Chen C, Nong Z, Xie Q, et al. (2017). 2-Dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione inhibits the growth and metastasis of breast carcinoma in mice. Scientific reports, 7(1), 6704.
- Lai LH, Fu QH, Liu Y, et al. (2012). Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model. Acta Pharmacol Sin., 33(4), 523-530.
- Wu H, Chen L, Zhu F, Han X, Sun L, Chen K. (2019). The cytotoxicity effect of resveratrol: cell cycle arrest and induced apoptosis of breast cancer 4T1 cells. Toxins, 11(12), 731.
- Jiang PD, Zhao YL, Deng XQ, et al. (2010). Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomed Pharmacother., 64(9), 609-614.
Details
| Primary Language | English |
|---|---|
| Subjects | Veterinary Sciences (Other) |
| Journal Section | Research |
| Authors | |
| Publication Date | June 30, 2025 |
| Submission Date | March 26, 2025 |
| Acceptance Date | May 20, 2025 |
| Published in Issue | Year 2025 Volume: 18 Issue: 1 |
