Alhoshani Norah M, Al-Johani Norah S, Alkeraishan Nora, Alarifi Saud, Alkahtani Saad
Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Saudi J Biol Sci. 2022 Sep;29(9):103392. doi: 10.1016/j.sjbs.2022.103392. Epub 2022 Jul 25.
Colon cancer (CC) is among the most frequent human cancers. Although, there is improvement in diagnostic techniques and existing treatment possibilities. Still, there is an unmet need for a novel treatment regimen that will improve the patient's quality of life. Here, the role of lycopene as an adjuvant therapy with 5-fluorouracil (5-FU) was explored in Caco2 colon cancer cells. Cells were exposed to a dose (3 µg/ml) of 5-FU and three doses (60, 90, 120 µg/ml) of lycopene either alone or as a mixture with 5-FU. Cytotoxicity, genotoxicity, oxidative stress, gene expression, and apoptotic parameters were investigated in this study. Findings showed that 5-FU or lycopene alone induced a dose-dependent increase in cytotoxicity which was slightly reduced in lycopene mixtures. Apoptotic assays showed that 5-FU induced a significant level of apoptosis but not necrosis. However, a lycopene mixture with 5-FU enhanced 5-FU triggered apoptosis and promoted necrosis. The mixtures were also shown to suppress mitochondrial membrane potential while gene expression analyses showed the induction of Bax expression upon exposure to mix 90 exhibited the highest Bax to Bcl-2 ratio and caspase 3 and 9 gene expression. Furthermore, the mixture treatment also inhibited cell migration in the wound healing assay compared to 5-FU alone. In conclusion, lycopene was found to sensitize Caco 2 cell lines to 5-FU treatment by inducing the expression of apoptotic genes. This, coupled with lycopene suppression of cytotoxicity and cell migration, indicates lycopene may be a promising candidate for adjuvant therapy involving 5-FU in CC.
结肠癌(CC)是人类最常见的癌症之一。尽管诊断技术和现有治疗方法有所改进,但对于能改善患者生活质量的新型治疗方案仍有未满足的需求。在此,研究了番茄红素作为5-氟尿嘧啶(5-FU)辅助疗法在Caco2结肠癌细胞中的作用。细胞分别单独暴露于3μg/ml剂量的5-FU和60、90、120μg/ml三个剂量的番茄红素,或与5-FU混合暴露。本研究调查了细胞毒性、遗传毒性、氧化应激、基因表达和凋亡参数。结果表明,单独使用5-FU或番茄红素均可诱导细胞毒性呈剂量依赖性增加,而在番茄红素混合物中这种增加略有降低。凋亡检测显示,5-FU可诱导显著水平的凋亡,但无坏死。然而,番茄红素与5-FU的混合物增强了5-FU引发的凋亡并促进了坏死。混合物还显示出抑制线粒体膜电位,而基因表达分析表明,暴露于混合物90时Bax表达的诱导表现出最高的Bax与Bcl-2比值以及半胱天冬酶3和9的基因表达。此外,与单独使用5-FU相比,混合物处理在伤口愈合试验中也抑制了细胞迁移。总之,发现番茄红素通过诱导凋亡基因的表达使Caco 2细胞系对5-FU治疗敏感。这一点,再加上番茄红素对细胞毒性和细胞迁移的抑制作用,表明番茄红素可能是CC中涉及5-FU的辅助治疗的有前景的候选药物。