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Chemomodulatory Effect of the Marine-Derived Metabolite 'Terrein' on the Anticancer Properties of Gemcitabine in Colorectal Cancer Cells
- Source :
- Marine Drugs, Vol 21, Iss 5, p 271 (2023)
- Publication Year :
- 2023
- Publisher :
- MDPI AG, 2023.
-
Abstract
- Background: 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. Methods: 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 (pO2 ≤ 1%) conditions. Further analysis via flow cytometry was carried out in addition to quantitative gene expression and 1HNMR metabolomic analysis. Results: 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. Conclusions: 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.
Details
- Language :
- English
- ISSN :
- 16603397
- Volume :
- 21
- Issue :
- 5
- Database :
- Directory of Open Access Journals
- Journal :
- Marine Drugs
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5fded4794d04bdd86ef56d4fcca3e83
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/md21050271