2. Academic Validation
  3. Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation

Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation

  • Bioorg Med Chem Lett. 2018 Sep 1;28(16):2688-2692. doi: 10.1016/j.bmcl.2018.04.008.
Kristopher E Boyle 1,  Dale L Boger 2,  Andrew Wroe 3,  Marcelo Vazquez 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Loma Linda University, 24745 Anderson St., Loma Linda, CA 92354, United States.
  • 2 Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 Torrey Pines Rd., La Jolla, CA 92037, United States.
  • 3 Loma Linda University Medical Center, Radiation Medicine Dept., 11234 Anderson St., Loma Linda, CA 92354, United States.
  • 4 Loma Linda University Medical Center, Radiation Medicine Dept., 11234 Anderson St., Loma Linda, CA 92354, United States. Electronic address: [email protected].
PMID: 29650288 DOI: 10.1016/j.bmcl.2018.04.008
Abstract

New treatment modalities for glioblastoma multiforme (GBM) are urgently needed. Proton therapy is considered one of the most effective forms of radiation therapy for GBM. DNA alkylating agents such as temozolomide (TMZ) are known to increase the radiosensitivity of GBM to photon radiation. TMZ is a fairly impotent agent, while duocarmycin SA (DSA) is an extremely potent cytotoxic agent capable of inducing a sequence-selective alkylation of duplex DNA. Here, the effects of sub-nM concentrations of DSA on the radiosensitivity of a human GBM cell line (U-138) to proton irradiation were examined. Radiation sensitivity was determined by viability, Apoptosis, necrosis and clonogenic assays. DSA concentrations as low as 0.001 nM significantly sensitized U-138 cells to proton irradiation. DSA demonstrates synergistic cytotoxicity against GBM cells treated with proton radiation in vitro, which may represent a novel therapeutic alternative for the treatment of GBM.

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