Combretastatin A-4 (CA-4) Induce P-53 Independent Apoptosis in Glioblastoma Cell Line (U-87MG)

سال انتشار: 1398
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 409

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شناسه ملی سند علمی:

NIMED03_173

تاریخ نمایه سازی: 7 آبان 1398

چکیده مقاله:

Glioblastoma is the most prevalent primary malignant brain tumor. Survival is mostly less than one year, and most patients die within twoyears. Standard therapy includes surgical resection and generally followed by radiotherapy and chemotherapy. CA4 as an antimitotic agent can strongly cause vascular shutdown and cell death in tumors by binding the colchicine binding site of tubulin to block microtubuleassembly. The aim of this stud was to investigate the apoptotic and cytotoxic effect of CA4 in glioblastoma multiforme (U87) cell line. Materials and Methods: Cellular cytotoxicity was measured by rezasurin assay and intracellular active oxygen species were measuredusing DCFDA (2 ‘and 7’-dichloro fluorescein diacetate) assay kit. In addition, apoptotic cells were detected with an Annexin V-FITC early apoptosis staining and cell cycle assay was investigated by propidium iodide (PI). Furthermore, Reatime PCR used to detect the alterationin gene expression of Apoptotic genes. Results: CA4 reduced the proliferation of U87 cells in a concentrationdependent manner. IC50 was 14 and 12.5 μg/mL after 24 and 48 hours, respectively. No significant increase observed in reactive oxygen spices level. Cell cycle distribution analysis showed significant increase in cell population in sub G1 area in concentration-dependent manner. Moreover, Anexin/PI analysis showed an increase in apoptotic cells after treatment by CA4. Significant alteration is not observed in gene expression of Bax, Bcl-2, and P-53. Conclusion: The study show that CA-4 can induce apoptosis in glioblastoma cells which seems it is p53-independent.

نویسندگان

Mostafa Karimi Roshan

Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Sajjad SahabNegah

Department of Neurosciences, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Amir Reza Afshari

Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Mohammad Soukhtanloo

Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran