Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an
Dong-Lin Yang1,2, Yong Li1, Shui-Qing Ma1
1College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing University of Arts and Sciences, Chongqing 402160, China.
Abstract:
Colorectal cancer (CRC) is the most common intestinal malignancy, and nearly 70% of patients with this cancer develop metastatic disease. In the present study, we synthesized a novel compound, termed N-(3-(5,7-dimethylbenzo [d]oxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#), and found that it exhibits antiproliferative capability in suppressing the proliferation and growth of CRC cell lines. Furthermore, compound 275# triggered caspase 3-mediated intrinsic apoptosis of mitochondria and autophagy initiation. An investigation of the molecular mechanisms demonstrated that compound 275# induced intrinsic apoptosis, and autophagy initiation was largely mediated by increasing the levels of the intracellular accumulation of reactive oxygen species (ROS) in CRC cells. Taken together, these data suggest that ROS accumulation after treatment with compound 275# leads to mitochondria-mediated apoptosis and autophagy activation, highlighting the potential of compound 275# as a novel therapeutic agent for the treatment of CRC.
Insights
A novel compound, N-(3-(5,7-dimethylbenzo [d]oxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#), effectively suppresses colorectal cancer (CRC) cell growth. It induces apoptosis and autophagy via reactive oxygen species (ROS) accumulation, showing therapeutic potential for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Colorectal cancer (CRC) is a leading cause of cancer death, with a high rate of metastatic disease.
- Effective therapeutic strategies for advanced CRC remain a critical unmet need.
Purpose of the Study:
- To synthesize and evaluate a novel compound (compound 275#) for its antiproliferative activity against colorectal cancer cell lines.
- To elucidate the molecular mechanisms underlying the anti-cancer effects of compound 275#.
Main Methods:
- Synthesis of N-(3-(5,7-dimethylbenzo [d]oxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#).
- Assessment of antiproliferative effects on CRC cell lines.
- Analysis of apoptosis induction (caspase 3-mediated) and autophagy initiation.
- Investigation of reactive oxygen species (ROS) levels and their role in the observed effects.
Main Results:
- Compound 275# demonstrated significant antiproliferative capability against CRC cell lines.
- Treatment with compound 275# induced caspase 3-mediated intrinsic apoptosis and autophagy.
- The compound increased intracellular ROS accumulation, which mediated apoptosis and autophagy.
Conclusions:
- Compound 275# exhibits potent anti-cancer properties against colorectal cancer.
- ROS-mediated mitochondrial apoptosis and autophagy activation are key mechanisms of action for compound 275#.
- Compound 275# represents a promising novel therapeutic candidate for CRC treatment.
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