Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, United Arab Emirates.
Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11591, Egypt.
Mar Drugs. 2023 Apr 26;21(5):271. doi: 10.3390/md21050271.
Terrein (Terr) is a bioactive marine secondary metabolite that possesses antiproliferative/cytotoxic properties by interrupting various molecular pathways. Gemcitabine (GCB) is an anticancer drug used to treat several types of tumors such as colorectal cancer; however, it suffers from tumor cell resistance, and therefore, treatment failure.
The potential anticancer properties of terrein, its antiproliferative effects, and its chemomodulatory effects on GCB were assessed against various colorectal cancer cell lines (HCT-116, HT-29, and SW620) under normoxic and hypoxic (pO ≤ 1%) conditions. Further analysis via flow cytometry was carried out in addition to quantitative gene expression and HNMR metabolomic analysis.
In normoxia, the effect of the combination treatment (GCB + Terr) was synergistic in HCT-116 and SW620 cell lines. In HT-29, the effect was antagonistic when the cells were treated with (GCB + Terr) under both normoxic and hypoxic conditions. The combination treatment was found to induce apoptosis in HCT-116 and SW620. Metabolomic analysis revealed that the change in oxygen levels significantly affected extracellular amino acid metabolite profiling.
Terrein influenced GCB's anti-colorectal cancer properties which are reflected in different aspects such as cytotoxicity, cell cycle progression, apoptosis, autophagy, and intra-tumoral metabolism under normoxic and hypoxic conditions.
特瑞安（Terr）是一种具有生物活性的海洋次生代谢产物，通过阻断多种分子途径具有抗增殖/细胞毒性作用。吉西他滨（GCB）是一种用于治疗多种肿瘤的抗癌药物，如结直肠癌；然而，它会产生肿瘤细胞耐药性，因此治疗失败。
在常氧和缺氧（pO ≤ 1%）条件下，评估特瑞安对各种结直肠癌细胞系（HCT-116、HT-29 和 SW620）的潜在抗癌特性、其抗增殖作用以及对 GCB 的化学调节作用。此外，还进行了定量基因表达和 HNMR 代谢组学分析。
在常氧条件下，联合治疗（GCB + Terr）在 HCT-116 和 SW620 细胞系中的作用是协同的。在 HT-29 中，当细胞在常氧和缺氧条件下用（GCB + Terr）处理时，作用是拮抗的。联合治疗被发现诱导 HCT-116 和 SW620 细胞凋亡。代谢组学分析表明，氧水平的变化显著影响细胞外氨基酸代谢产物谱。
特瑞安影响 GCB 的抗结直肠癌特性，这些特性反映在常氧和缺氧条件下的细胞毒性、细胞周期进展、细胞凋亡、自噬和肿瘤内代谢等不同方面。
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