Biological Activity of a Thiobarbituric Acid Compound in Neuroblastomas.

Abstract

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.

• Authors: Sang Y Lee, Becky Slagle-Webb, Arun K Sharma, James R Connor
• Journal: Anticancer research (Anticancer Res) Vol. 41 Issue 3 Pg. 1171-1181 (Mar 2021) ISSN: 1791-7530 [Electronic] Greece
• PMID: 33788708 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antineoplastic Agents
• HSP27 Heat-Shock Proteins
• Thiobarbiturates
• Proto-Oncogene Proteins c-akt
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Child
• Child, Preschool
• Female
• Fibroblasts (drug effects)
• HSP27 Heat-Shock Proteins (physiology)
• Humans
• JNK Mitogen-Activated Protein Kinases (physiology)
• Male
• Mice
• Neuroblastoma (drug therapy, pathology)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (physiology)
• Thiobarbiturates (pharmacology, therapeutic use)