Acriflavine enhances radiosensitivity of colon cancer cells through endoplasmic reticulum stress-mediated apoptosis

The International Journal of Biochemistry & Cell Biology
Min-Jin LimJie-Young Song

Abstract

Radiotherapy (RT) is one of the most effective tools in the clinical treatment of cancer. Because the tumor suppressor p53 plays a central role in radiation-mediated responses, including cell cycle-arrest and apoptosis, a number of studies have suggested that p53 could be a useful therapeutic target of anti-cancer agents. Accordingly, we sought to discover a new agent capable of increasing p53 activity. HCT116 colon cancer cells, containing wild-type p53, were stably transfected with a p53 responsive-luciferase (p53-Luc) reporter gene. A cell-based high-throughput screen of 7920 synthetic small molecules was performed in duplicate. Of the screened compounds, acriflavine (ACF) significantly increased p53-Luc activity in a concentration-dependent manner without causing toxicity. Pretreatment with ACF enhanced the induction of p53 protein expression and phosphorylation on serine 15 by γ-irradiation. Clonogenic assays showed that ACF pretreatment also potentiated radiation-induced cell death. The combination of irradiation and ACF treatment induced mitochondrial release of cytochrome c and significant activation of caspase-3 with PARP cleavage in colon cancer cells, demonstrating typical apoptotic cell death. Combined treatment wit...Continue Reading

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Citations

Aug 6, 2013·International Journal of Molecular Sciences·Ronald-Allan M PanganibanRegina M Day
Jun 26, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jingzhang FanZhenggang Bi
Jun 30, 2019·The Journal of Pharmacology and Experimental Therapeutics·Seung-Youn JungJie-Young Song
Jul 16, 2020·Journal of Cellular and Molecular Medicine·Rawan HallalFrédéric Mazurier

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