2. Academic Validation
  3. Seco-Duocarmycin SA in Aggressive Glioblastoma Cell Lines

Seco-Duocarmycin SA in Aggressive Glioblastoma Cell Lines

  • Int J Mol Sci. 2025 Mar 19;26(6):2766. doi: 10.3390/ijms26062766.
Ann Morcos 1 2,  Yeonkyu Jung 1 2,  Ryan N Fuller 3,  Antonella Bertucci 1 4,  Amy Nguyen 5,  Quanqing Zhang 5,  Tobias Emge 1 2,  Kristopher E Boyle 6,  Nathan R Wall 1 2,  Marcelo Vazquez 1 7
Affiliations

Affiliations

  • 1 Department of Radiation Medicine, James M. Slater, MD Proton Treatment & Research Center, Loma Linda University Health, Loma Linda, CA 92350, USA.
  • 2 Division of Biochemistry, Department of Basic Science, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
  • 3 Department of Biological Sciences, California Baptist University, Riverside, CA 92504, USA.
  • 4 Nuclear Response & Analysis, Canadian Nuclear Laboratories, Chalk River, ON K0J 1J0, Canada.
  • 5 Proteomics Core, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA.
  • 6 School of Pharmacy, Loma Linda University, Loma Linda, CA 92399, USA.
  • 7 Radiobiology & Health, Canadian Nuclear Laboratories, Chalk River, ON K0J 1J0, Canada.
PMID: 40141405 DOI: 10.3390/ijms26062766
Abstract

Glioblastoma multiforme (GBM) is among the most lethal primary brain tumors and is characterized by significant cellular heterogeneity and resistance to conventional therapies. This study investigates the efficacy of seco-duocarmycin SA (seco-DSA), a novel DNA alkylating agent. Initial investigations using a colony formation assay revealed that seco-DSA exhibits remarkable potential with IC50 values lower than its natural DSA counterpart. Cell viability assay indicated that LN18 cells showed a markedly greater sensitivity to DSA than T98G cells. Furthermore, seco-DSA achieved its full cytotoxic effect within 8 h of drug incubation in GBM cell lines. Although seco-DSA induced a concentration-dependent increase in apoptotic cell death, the extent of Apoptosis did not fully account for the observed decrease in cell viability. Instead, seco-DSA treatment resulted in significant cell cycle arrest in S and G2/M phases. These findings suggest that seco-DSA's cytotoxicity in GBM cells is primarily due to its ability to disrupt cell cycle progression, though the precise mechanisms of action remain to be fully established, and further research is needed. Proteomic analysis of treated cells also indicates dysregulation of proteins involved in senescence, Apoptosis, and DNA repair, alluding to seco-DSA-induced arrest as a major mechanism of GBM disruption. Data are available via ProteomeXchange with the dataset identifier "PXD061023". Our reports promote the future exploration of seco-DSA's therapeutic potential, representing a critical step toward developing a more targeted and effective treatment for GBM.

Keywords

cellular mechanisms; duocarmycin; glioblastoma multiforme; potency; proof of concept; resistance; seco-DSA.

Figures
Products