Enhanced in vitro tumoricidal effects of 5-Fluorouracil, thymoquinone, and active vitamin D3 triple therapy against colon cancer cells by attenuating the PI3K/AKT/mTOR pathway

• Published in: Life sciences (1973) 2022-05, Vol.296, p.120442-120442, Article 120442
• Main Authors: Idris, Shakir, Refaat, Bassem, Almaimani, Riyad A., Ahmed, Hussain G., Ahmad, Jawwad, Alhadrami, Mai, El-Readi, Mahmoud Zaki, Elzubier, Mohamed E., Alaufi, Haneen A.A., Al-Amin, Badriah, Alghamdi, Ahmad A., Bahwerth, Fayez, Minshawi, Faisal, Kabrah, Saeed M., Aslam, Akhmed
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 25-Hydroxyvitamin D; 5-Fluorouracil; AKT protein; Anticancer properties; Antioxidants; Apoptosis; Bcl-2 protein; Calcitriol; Cell cycle; Chemoresistance; Colon; Colon cancer; Colorectal carcinoma; Cyclin-dependent kinase inhibitor p21; Glutathione; Malignancy; Metastases; Metastasis; Oxidants; Oxidative stress; Oxidizing agents; PTEN protein; Therapy; Thymoquinone; TOR protein; Vitamin D3
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.120442

This study measured the effects of 5-Fluorouracil (5-FU), calcitriol (VD3), and/or thymoquinone (TQ) single/dual/triple therapies on cell cycle progression, apoptosis, inhibition of the PI3K/AKT/mTOR pathway, and oxidative stress against colorectal cancer (CRC). The HT29, SW480 and SW620 cell lines were treated with 5-FU (50 μM), VD3 (25 μM), and TQ (75 μM), alone or combined for 12 h, prior to cell cycle/apoptosis analyses. TQ monotherapy had greater anticancer effects to active VD3 or 5-FU, revealing higher expression of p21/p27/PTEN/BAX/Cyto-C/Casp-3 and increased levels of total glutathione, with inhibitions in CCND1/CCND3/BCL-2 and PI3K/AKT/mTOR molecules, alongside higher rates of apoptosis in HT29, SW480 and SW620 cells (P