Potentiation of Anticancer Activity of G2/M Blockers by Mild Hyperthermia

Abstract

Background/aim: Hyperthermia (HT), combined with chemotherapy, has been used to treat various types of cancer. This study aimed to investigate the HT-sensitivity of malignant and non-malignant cells, and then evaluate the combination effect of docetaxel (DTX) and a newly synthesized chromone derivative (compound A) with HT.

Materials and methods: The number of viable cells was determined using the MTT method. Cell cycle distribution was analyzed using a cell sorter, and DNA fragmentation pattern was detected using agarose gel electrophoresis.

Results: Among 12 cultured cells, oral squamous cell carcinoma (OSCC), especially Ca9-22 cells, and myelogenous leukemia cells showed higher sensitivity to HT than lung carcinoma and glioblastoma cell lines, while normal oral cells were the most resistant. Cytotoxicity of DTX on Ca9-22 cells was maximum at 41-42°C and 45~60 min exposure to HT. DXT, compound A, and HT induced G₂/M arrest of Ca-22 cells. Mild HT enhanced the DTX- and compound A-induced subG₁ arrest, in a synergistic fashion.

Conclusion: The combination G₂/M blockers and mild-HT can potentially be used for the treatment of OSCC.

Keywords: G2/M blocker; Oral squamous cell carcinoma; chromone derivatives; mild hyperthermia; synergism.