Glucosamine induces autophagic cell death through the stimulation of ER stress in human glioma cancer cells.
Autophagy can promote cell survival or death, but the molecular basis of its dual role in cancer is not well understood. Here, we report that glucosamine induces autophagic cell death through the stimulation of endoplasmic reticulum (ER) stress in U87MG human glioma cancer cells. Treatment with glucosamine reduced cell viability and increased the expression of LC3 II and GFP-LC3 fluorescence puncta, which are indicative of autophagic cell death. The glucosamine-mediated suppression of cell viability was reversed by treatment with an autophagy inhibitor, 3-MA, and interfering RNA against Atg5. Glucosamine-induced ER stress was manifested by the induction of BiP, IRE1alpha, and phospho-eIF2alpha expression. Chemical chaperon 4-PBA reduced ER stress and thereby inhibited glucosamine-induced autophagic cell death. Taken together, our data suggest that glucosamine induces autophagic cell death by inducing ER stress in U87MG glioma cancer cells and provide new insight into the potential anticancer properties of glucosamine.
Hwang
Mi-Sun
MS
Chronic Disease Research Center, Keimyung University, Daegu, Republic of Korea.
Baek
Won-Ki
WK
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D005944:Glucosamine / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism
C502778:ATG5 protein, human; D000970:Antineoplastic Agents; D000071187:Autophagy-Related Protein 5; C539791:Bax-inhibiting peptide, BIP; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D009842:Oligopeptides; D049452:Green Fluorescent Proteins; D005944:Glucosamine