Efficacy In Vitro of Caffeine and Valproic Acid on Patient-Derived Undifferentiated Pleomorphic Sarcoma and Rhabdomyosarcoma Cell Lines

Background/Aim: We have previously reported that caffeine (CAF) can enhance chemotherapy efficacy of bone and soft-tissue sarcoma established cell lines via cell-cycle perturbation. We subsequently tested the combination of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, with caffeine on established human osteosarcoma cells in vitro. Both VPA and CAF caused concentration-dependent cell death of the osteosarcoma cell lines in vitro, and their combination was synergistic. We subsequently established patient-derived cell lines from undifferentiated pleomorphic sarcoma (UPS) and rhabdomyosarcoma (RMS), both of which are recalcitrant cancers. These cell lines are termed AC-UPS01 and AC-RMS01, respectively. Materials and Methods: In the present study, we tested CAF and VPA and their combination on the two patient-derived sarcoma cell lines. Cell survival after a 72 h exposure to each drug was determined by the WST-8 assay. IC50 values were calculated for each drug. Results: CAF and VPA caused concentration-dependent cytocidal efficacy for both cell lines. The IC50 for CAF for AC-UPS01 was 2.02 +/- 0.22 mM. The IC50 for VPA for AC-UPS01 was 9.54 +/- 1.44 mM. The IC50 for CAF for AC-RMS01 was 2.37 +/- 0.48 mM. The IC50 for VPA for AC-RMS01 was 2.13 +/- 0.20 mM. Synergistic efficacy of combination treatment of CAF and VPA was also observed for both cell lines. Conclusion: The results of the present study suggest that CAF and VPA may be useful in the treatment of recalcitrant sarcoma.