Gossypol enhances radiation-induced autophagy in glioblastoma multiforme

Abstract

Malignant gliomas (glioblastoma multiforme) are the most aggressive of the primary brain tumors. Radiotherapy is an important tool for treatment of cancer but malignant gliomas are usually resistant to radiotherapy and other adjuvant therapies. Thus new drugs are needed to increase the efficiency of radiotherapy in order to improve the therapeutic outcome of tumor patients. Recent investigations showed that gossypol, natural polyphenolic compound produced by cotton plants, is a promising agent against solid tumors. The current study was defined to evaluate whether the combinatorial effect of radiation and gossypol would induce higher level of cell death on human glioma cell line U-87 MG than single agent treatment and its possible mechanism of action. Clonogenic survival assay showed that ionizing radiation plus gossypol significantly inhibited clonogenic growth of irradiated cells as compared with either treatment alone. Acridine orange/etidium bromide staining confirmed that there was no significant increase in necrotic and apoptotic cells, but irradiated cells in combination with gossypol showed a significant increase in accumulation of acidic vesicular organelle. The results obtained herein indicated that gossypol is a promising drug that induced autophagic cell death in radioresistant malignant glioma.