2. Academic Validation
  3. The amide derivative of anticopalic acid induces non-apoptotic cell death in triple-negative breast cancer cells by inhibiting FAK activation

The amide derivative of anticopalic acid induces non-apoptotic cell death in triple-negative breast cancer cells by inhibiting FAK activation

  • Sci Rep. 2023 Aug 18;13(1):13456. doi: 10.1038/s41598-023-40669-6.
Pornsuda Chawengrum # 1,  Natthaorn Luepongpatthana # 2,  Sanit Thongnest 3 4,  Jitnapa Sirirak 5,  Jutatip Boonsombat 6 7,  Kriengsak Lirdprapamongkol 8 9,  Siriporn Keeratichamroen 10,  Patcharin Kongwaen 3,  Phreeranat Montatip 10,  Prasat Kittakoop 1 3 4,  Jisnuson Svasti 2 10,  Somsak Ruchirawat 1 3 4
Affiliations

Affiliations

  • 1 Chemical Biology Program, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, Thailand.
  • 2 Applied Biological Sciences Program, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, Thailand.
  • 3 Laboratory of Natural Products, Chulabhorn Research Institute, Bangkok, Thailand.
  • 4 Center of Excellence on Environmental Health and Toxicology (EHT), Office of the Permanent Secretary (OPS), Ministry of Higher Education, Science, Research and Innovation (MHESI), Bangkok, Thailand.
  • 5 Department of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom, Thailand.
  • 6 Laboratory of Natural Products, Chulabhorn Research Institute, Bangkok, Thailand. [email protected].
  • 7 Center of Excellence on Environmental Health and Toxicology (EHT), Office of the Permanent Secretary (OPS), Ministry of Higher Education, Science, Research and Innovation (MHESI), Bangkok, Thailand. [email protected].
  • 8 Center of Excellence on Environmental Health and Toxicology (EHT), Office of the Permanent Secretary (OPS), Ministry of Higher Education, Science, Research and Innovation (MHESI), Bangkok, Thailand. [email protected].
  • 9 Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand. [email protected].
  • 10 Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand.
  • # Contributed equally.
PMID: 37596365 DOI: 10.1038/s41598-023-40669-6
Abstract

Anticopalic acid (ACP), a labdane type diterpenoid obtained from Kaempferia elegans rhizomes, together with 21 semi-synthetic derivatives, were evaluated for their Cancer cytotoxic activity. Most derivatives displayed higher cytotoxic activity than the parent compound ACP in a panel of nine Cancer cell lines. Among the tested compounds, the amide 4p showed the highest cytotoxic activity toward leukemia cell lines, HL-60 and MOLT-3, with IC50 values of 6.81 ± 1.99 and 3.72 ± 0.26 µM, respectively. More interestingly, the amide derivative 4l exhibited cytotoxic activity with an IC50 of 13.73 ± 0.04 µM against the MDA-MB-231 triple-negative breast Cancer cell line, which is the most aggressive type of breast Cancer. Mechanistic studies revealed that 4l induced cell death in MDA-MB-231 cells through non-apoptotic regulated cell death. In addition, western blot analysis showed that compound 4l decreased the phosphorylation of FAK protein in a concentration-dependent manner. Molecular docking simulations elucidated that compound 4l could potentially inhibit FAK activation by binding to a pocket of FAK kinase domain. The data suggested that compound 4l could be a potential FAK Inhibitor for treating triple-negative breast Cancer and worth being further investigated.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-156026
    FAK Inhibitor
    FAK