LAUSR

Various cancer cells require massive amounts of glucose as an energy source for their dysregulated growth. Although D-allose, a rare sugar, inhibits tumor cell growth via inhibition of glucose uptake, a few cells can survive after treatment. However, the mechanism by which D-allose-resistant cells are generated remains unclear. Here, we investigated the properties of D-allose-resistant cells and evaluated the efficacy of combined treatment with this rare sugar and antitumor drugs. To this end, we established a D-allose-resistant tumor cell line and prepared a C57BL/6J mouse tumor xenograft model using Lewis lung carcinoma (LLC) cells. Xenograft-bearing mice were treated with D-allose (9 g/kg) and/or hydroxychloroquine (HCQ, 60 mg/kg), an autophagy inhibitor, for two weeks. Although D-allose inhibited LLC cell growth in a dose-dependent manner, a few cells survived. The upregulation of LC3-II, a classical autophagy marker, and the downregulation of mTOR and its downstream molecule Beclin1 were observed in established D-allose-resistant LLC cells, which were more sensitive to cell death induced by HCQ. Similarly, in the tumor xenograft model, the tumor volume in mice co-treated with D-allose and HCQ was considerably smaller than that in untreated or HCQ-treated mice. Importantly, the administration of D-allose induced autophagy selectively at the tumor site of the xenograft-bearing mice. These results provide a new therapeutic strategy targeting autophagy which is induced in tumor cells by D-allose administration, and may be used to improve therapies for lung cancer.