The therapeutic potential of gamma-Al2O3 nanoparticle containing 5-fluorouracil in the treatment of colorectal cancer

• Main Authors: Fasihi, Khadije, Amerizadeh, Forouzan, Sabbaghzadeh, Reihaneh, Heydari, Maryam, Rahmani, Farzad, Mostafapour, Asma, Khazaei, Majid, Rasouli, Elisa, Hassanian, Seyed Mahdi, Ferns, Gordon A., Rezayi, Majid, Avan, Amir
• Format: Article
• Published: Churchill Livingstone 2022
• Subjects: QH301 Biology; RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Online Access: http://eprints.um.edu.my/42342/
• Institution: Universiti Malaya

5-Fluorouracil (5-FU) is being used in the treatment of several malignancies, but side effects are often reported and include: diarrhea, vomiting, nausea, poor appetite, watery eyes, and photophobia. We have developed and tested the cytotoxic activity of nanocrystalline powder of gamma-alumina (gamma-Al2O3) containing 5-FU in two-dimensional and three-dimensional (3D) CRC cell culture. gamma-Al2O3 was prepared using a facile sol-gel method. The physicochemical properties of nanoparticles were investigated by Fourier Transform Infrared (FTIR) analysis, Field Emission Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray Analysis (EDXA). Moreover, the particle size was monitored by Transmission Electron Microscopy (TEM). We used MTT and a scratch assay to assess the antiproliferative and anti-migratory of this agent. The effect of gamma-Al2O3-5-FU on SOD, MDA, and total-thiols levels were evaluated. We assessed the expression of apoptotic markers in mRNA or proteins by RT-PCR and ELISA respectively. gamma-Al2O3-5-FU inhibited cell growth in two-dimensional (2D) and three-dimensional (3D) cell culture and increased apoptosis as detected by DAPI stainning via modulation of caspases, BAx, BCl2 and cyclinD1 . gamma-Al2O3-5-FU also reduced the migratory activity of CRC cells relative to untreated controls. gamma-Al2O3-5-FU increased the level of MDA, while reducing the level of SOD and total-thiols as well as inflamatory markers (e.g., TNF-s and IL-6). Our study demonstrated that gamma-Al2O3-5-FU inhibited cell growth and migration, indicating its potential value in the treatment of colorectal cancer.