3742 - Boosting Antiproliferative Outcomes in Oral Cancer via Combined X-Ray and 6-n-butoxy-10-nitro-12,13-dioxa-11-azatricyclo[7.3.1.0^2,7]trideca-2,4,6,10-tetraene Therapy

J. Y. Tang; Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Taiwan

Purpose/Objective(s): This study investigates the synergistic effect of X-ray radiation and SK2(6-n-butoxy-10-nitro-12,13-dioxa-11-azatricyclo[7.3.1.0^2,7]trideca-2,4,6,10-tetraene) on oral cancer cells, aiming to elucidate the mechanisms by which SK2 enhances the sensitivity of these cells to X-ray induced oxidative stress, leading to increased apoptosis. Materials/

Methods: The research employed two oral cancer cell lines (Ca9-22 and CAL 27) alongside a normal cell line (Smulow–Glickman, S-G), treating them with X-rays (12 Gy), SK2 (10 µg/mL), or a combination thereof. Assessment of cell health and mortality involved flow cytometry to measure cell viability, cycle phases, apoptosis rates, caspase activation, and oxidative stress (ROS, MitoSOX, MMP, GSH) alongside DNA damage (?H2AX, 8-OHdG). Additionally, the role of ROS was interrogated using the antioxidant N-acetylcysteine.
Results: Treatment with X-ray and SK2 in combination proved significantly more lethal to oral cancer cells than to normal cells, with increased apoptosis, caspase 3/8 activation, alterations in cell cycle distribution (notably in subG1 and G2/M phases), and enhanced ROS production alongside diminished MMP. Noteworthy was the differential activation of caspase 9 across cancer cell lines. DNA damage markers escalated post-treatment, indicating potentiated cellular stress. Counteracting effects via N-acetylcysteine suggested ROSs critical role.
Conclusion: The adjunctive use of SK2 with X-rays introduces a potent ROS-mediated strategy against oral cancer, decelerating cellular proliferation, amplifying mortality, and inducing substantial DNA damage while sparing normal cells. These findings position SK2 as a promising augment to radiation therapy in oral cancer management. Future studies should probe the variable responsiveness among oral cancer cell lines and validate these outcomes in vivo.