TY - JOUR T1 - Biological Activity of a Thiobarbituric Acid Compound in Neuroblastomas JF - Anticancer Research JO - Anticancer Res SP - 1171 LP - 1181 DO - 10.21873/anticanres.14874 VL - 41 IS - 3 AU - SANG Y. LEE AU - BECKY SLAGLE-WEBB AU - ARUN K. SHARMA AU - JAMES R. CONNOR Y1 - 2021/03/01 UR - http://ar.iiarjournals.org/content/41/3/1171.abstract N2 - Background/Aim: We have previously reported the identification of the cytotoxic chemotype compound-I (CC-I) from a chemical library screening against glioblastoma. Materials and Methods: The biological activity of CC-I on drug-resistant neuroblastomas [e.g., HFE gene variant C282Y stably transfected human neuroblastoma SH-SY5Y cells (C282Y HFE/SH-SY5Y), SK-N-AS] was characterized using cell culture models and in vivo mouse tumor models. Results: CC-I had potent cytotoxicity on therapy-resistant neuroblastoma cells and limited cytotoxicity on human primary dermal fibroblast cells. In addition, CC-I showed a robust anti-tumor effect on therapy-resistant human neuroblastoma C282Y HFE/SH-SY5Y cells but not on SK-N-AS cells in a subcutaneous tumor model. CC-I induced phosphorylation of heat shock protein 27 (HSP27), protein kinase B (Akt), and c-Jun N-terminal kinase (JNK) in C282Y HFE/SH-SY5Y neuroblastoma cells. Conclusion: CC-I may be an effective therapeutic option for therapy-resistant neuroblastomas, especially if they express the C282Y HFE gene variant. Its anti-tumor effects are possibly through HSP27-Akt-JNK activation. ER -