Department of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Chemistry Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt.
Molecules. 2022 Oct 6;27(19):6624. doi: 10.3390/molecules27196624.
Inflammation prompts cancer development and promotes all stages of tumorigenesis. Calcitriol is a nutraceutical essential regulator for host health benefits. However, the influence of calcitriol on inflammatory mediators involved in cancer cells is not clear. This study aimed to assess the sensitivity of calcitriol alone and combined with capric acid, and identify the possible influence of calcitriol on inflammatory mediators. The colorectal cancer cell line (HCT116) was induced by LPS/TNF-α and the inflammation and metastatic mediators (IL-1β, IL-6, IL-17) were quantified in calcitriol and capric acid supplemented colon cancer cells. The mRNA and protein expression of MMP-2, NF-κB and COX-2 were quantified. The significant reduction in MMP-2 expression was confirmed at combination treatment by zymogram analysis. Our findings demonstrated the anti-inflammatory and anti-metastatic potentials of capric acid and calcitriol in individual exposure in a combination of human colon cancer cell lines (HCT116). These abilities may be due to the inhibition of COX-2 mediators and NF-κB transcription factor and reciprocally regulated MMP-2 and MMP-9 signaling pathways. These findings elucidate the activation of COX-2 and NF-κB via disruption of the cellular outer matrix could be considered a novel molecular target suitable for colorectal cancer therapy. This study confirmed that capric acid activates calcitriol sensitization in colon cancer cells and could be used as a successful supplement for intestinal diseases and colon aberrations.
炎症会促进癌症的发展，并促进肿瘤发生的所有阶段。钙三醇是一种对宿主健康有益的必需营养调节剂。然而，钙三醇对涉及癌细胞的炎症介质的影响尚不清楚。本研究旨在评估钙三醇单独和与癸酸联合使用的敏感性，并确定钙三醇对炎症介质的可能影响。用 LPS/TNF-α 诱导结肠癌细胞系 (HCT116)，并在添加钙三醇和癸酸的结肠癌细胞中定量炎症和转移介质 (IL-1β、IL-6、IL-17)。定量 MMP-2、NF-κB 和 COX-2 的 mRNA 和蛋白表达。通过酶谱分析证实联合治疗时 MMP-2 表达明显减少。我们的研究结果表明，癸酸和钙三醇在单独暴露和联合暴露于人结肠癌细胞系 (HCT116) 时具有抗炎和抗转移潜力。这些能力可能是由于抑制 COX-2 介质和 NF-κB 转录因子以及相互调节的 MMP-2 和 MMP-9 信号通路。这些发现阐明了通过破坏细胞外基质激活 COX-2 和 NF-κB 可以被认为是适合结直肠癌治疗的新的分子靶标。本研究证实，癸酸可激活结肠癌细胞中钙三醇的敏感性，可作为治疗肠道疾病和结肠异常的成功补充剂。
