A novel chalcone derivative exerts anticancer effects by promoting apoptotic cell death of human pancreatic cancer cells
- Bioorg Med Chem. 2023 Oct 1:93:117458. doi: 10.1016/j.bmc.2023.117458.
- 1. Research & Development Center, UMUST R&D Corporation, Seoul 01411, South Korea.
- 2. Seoul Center, Korea Basic Science Institute, Seoul 02841, South Korea.
- 3. Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea.
- 4. Research & Development Center, UMUST R&D Corporation, Seoul 01411, South Korea. Electronic address: [email protected].
- 5. Department of Nuclear Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul 07804, South Korea. Electronic address: [email protected].
Aggressive pancreatic Cancer is typically treated using chemotherapeutics to reduce the tumor pre-operatively and prevent metastasis post-operatively, as well as surgical approaches. In the present study, we synthesized a hydroxyl group-introduced chalcone derivative (1, IC50 = 32.1 μM) and investigated its potential as an Anticancer drug candidate by evaluating its apoptosis-promoting effects on BXPC-3 Cancer cells. The viability of BXPC-3 cells treated with 1 was measured using the water-soluble tetrazolium 1 reagent. BXPC-3 cells induced by 1 were stained with diverse probes or antibodies, such as ethidium homodimer-1, Hoechst, anti-Ki67, and MitoTracker. Protein expression was measured using an immunoblotting assay, and mRNA expression was determined using real-time polymerase chain reaction. Apoptotic molecular features, such as lipid accumulation and protein degradation, were monitored directly using stimulated Raman scattering microspectroscopy. Through incubation time- and concentration-dependent studies of 1, we found that it significantly reduced the proliferation and increased the number of apoptotic BXPC-3 cells. Compound 1 induced mitochondrial dysfunction, phosphorylation of p38, and Caspase 3 cleavage. These results indicate that 1 is a potential therapeutic agent for pancreatic Cancer, providing valuable insights into the development of new Anticancer drug candidates.