Abstract
Background: Radiation is one of the main modalities for the treatment of cancer. However, tumor resistance and recurrence are currently major clinical challenges. Here, we screened for the possible therapeutic effect of perylenequinone derivatives (PDs) administered in combination with radiotherapy in various tumor types both in vitro and in vivo by testing their impact on tumor initiating cells (TICs). Methods: U87, MCF7, HT29, A549 and PANC1 tumor cell lines were grown under standard culture conditions, or as non-adherent TIC-enriched cultures. Cultured cells were treated with 0.1-2µM of PDs Hypericin (Hy), Hypericin tetrasulfonate (HyTS) or Tetrabromo hypericin (TBrHy), and exposed to either single high-dose or fractionated daily-dose radiation. Cell viability was assessed. Furthermore, tumor growth of PANC1 and U87 cells which were implanted in mice that subsequently were injected with the PDs and exposed to local ionizing radiation was assessed. Results: Our results show that PDs significantly inhibited viability of irradiated tumor cells cultured in normal and TICenriched conditions of various cell lines. Moreover, TBrHy significantly delayed U87 and PANC1 tumor growth in mice receiving high-dose radiation.Conclusions: These results indicate that TIC viability can be used as a method to test radiosensitizing activity. As such, PDs could potentially be effective radiosensitizing agents that may target tumor cells and TICs, highlighting their potential therapeutic value.
Keywords: Hypericin, cancer stem cells, radiosensitizing agents, high-dose radiation, cell viability.
Graphical Abstract
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