Academic Journal
The Anticancer Effects of the Pro-Apoptotic Benzofuran-Isatin Conjugate (5a) Are Associated With p53 Upregulation and Enhancement of Conventional Chemotherapeutic Drug Efficiency in Colorectal Cancer Cell Lines
| العنوان: | The Anticancer Effects of the Pro-Apoptotic Benzofuran-Isatin Conjugate (5a) Are Associated With p53 Upregulation and Enhancement of Conventional Chemotherapeutic Drug Efficiency in Colorectal Cancer Cell Lines |
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| المؤلفون: | Mansoor-Ali Vaali-Mohammed, Maha-Hamadien Abdulla, Sabine Matou-Nasri, Wagdy M. Eldehna, M. Meeramaideen, Eslam B. Elkaeed, Mohammed El-Watidy, Noura S. Alhassan, Khayal Alkhaya, Omar Al Obeed |
| المصدر: | Frontiers in Pharmacology, Vol 13 (2022) |
| بيانات النشر: | Frontiers Media S.A. |
| سنة النشر: | 2022 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | colorectal cancer, epithelial-mesenchymal transition, synthetic compound, apoptosis, cell cycle, anticancer, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | The present study aimed to investigate in-depth a cytotoxic novel benzofuran-isatin conjugate (5a, 3-methyl-N'-(2-oxoindolin-3-ylidene)benzofuran-2-carbohydrazide) with promising potential anticancer activities in colorectal adenocarcinoma HT29 and metastatic colorectal cancer (CRC) SW620 cell lines. Thus, the primary cell events involved in tumorigenicity, tumor development, metastasis, and chemotherapy response were explored. Both CRC cell lines were exposed to different concentrations of Compound 5a and then subjected to real-time cell viability, migration, and invasion assays, colony formation and cytotoxicity assays, and flow cytometry for cell cycle analysis and apoptosis determination. Western blot and RT-qPCR were performed to assess the protein and transcript expression levels of epithelial-mesenchymal transition (EMT), cell cycle, and apoptosis markers. We showed that the Compound 5a treatment exhibited anticancer effects through inhibition of HT29 and SW620 cell viability, migration, and invasion, in a dose-dependent manner, which were associated with the upregulation of the tumor suppressor p53. Compound 5a also inhibited the colony formation ability of HT29 and SW620 cells and reversed EMT markers E-cadherin and N-cadherin expression. CRC cell exposure to Compound 5a resulted in a cell cycle arrest at the G1/G0 phase in HT29 cells and at the G2/M phase in SW620 cells, along with the downregulation of cyclin A1 expression, described to be involved in the S phase entry. Furthermore, Compound 5a-induced apoptosis was associated with the downregulation of the anti-apoptotic Bcl-xl marker, upregulation of pro-apoptotic Bax and cytochrome c markers, and increased mitochondrial outer membrane permeability, suggesting the involvement of mitochondria-dependent apoptosis pathway. In addition, the combination studies of Compound 5a with the main conventional chemotherapeutic drugs 5-fluorouracil, irinotecan, and oxaliplatin showed a more potent cytotoxic effect in both CRC cells than a single treatment. In ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1663-9812 |
| Relation: | https://www.frontiersin.org/articles/10.3389/fphar.2022.923398/full; https://doaj.org/toc/1663-9812; https://doaj.org/article/38e2d28db56743778898b51cd2db86f3 |
| DOI: | 10.3389/fphar.2022.923398 |
| الاتاحة: | https://doi.org/10.3389/fphar.2022.923398 https://doaj.org/article/38e2d28db56743778898b51cd2db86f3 |
| رقم الانضمام: | edsbas.5D0865C0 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16639812 |
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| DOI: | 10.3389/fphar.2022.923398 |