Sodium butyrate induces autophagy in colorectal cancer cells through LKB1/AMPK signaling

• Shunli Luo ^[1] ; Ziyin Li ^[1] ; Lianzhi Mao ^[1] ; Siqiang Chen ^[2] ; Suxia Sun ^[1]
  1. [1] Southern Medical University

     Southern Medical University

     China

     
  2. [2] Guangzhou Customs District, China
• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 75, Nº. 1 (February), 2019, págs. 53-63
• Idioma: inglés
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• Resumen

  • Butyrate is produced by the fermentation of undigested dietary fibers and acts as the promising candidate for cancer treatment. However, the mechanism underlying sodium butyrate (NaB)-induced autophagy in colorectal cancer is not yet completely understood. The expressions of LC3-II protein and mRNA were detected by western blot and quantitative RT-PCR in colorectal cancer (CRC) cell lines HCT-116 and HT-29, respectively. Autolysosome formation was observed by transmission electron microscope. AMPK and LKB1 were inhibited by chemical inhibitor or siRNAs and confirmed by western blot. NaB elevated the protein and mRNA expressions of LC3 in a dose-dependent manner. NaB treatment increased the formation of autolysosome and expression of phosphorylated liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC). Treatment with compound C (an inhibitor of AMPK) and siRNA-mediated knockdown of AMPK and LKB1 significantly attenuated NaB-induced autophagy in CRC cells. Collectively, these findings indicated that LKB1 and AMPK are critical for NaB-mediated autophagy and may act as the novel targets for colorectal cancer therapy in the future.