2. Academic Validation
  3. A novel chalcone derivative exerts anticancer effects by promoting apoptotic cell death of human pancreatic cancer cells

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.
Suji Baek 1,  Sanghee Nah 2,  Joo Yeon Park 1,  Sang Ju Lee 3,  Yong Gil Kang 1,  Seung Hae Kwon 2,  Seung Jun Oh 3,  Kang Pa Lee 4,  Byung Seok Moon 5
Affiliations

Affiliations

  • 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].
PMID: 37634418 DOI: 10.1016/j.bmc.2023.117458
Abstract

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.

Keywords

Apoptosis; Chalcone; Lipid accumulation; Pancreatic cancer; Stimulated Raman scattering microscopy.

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