D‑allose enhances the efficacy of hydroxychloroquine against Lewis lung carcinoma cell growth by inducing autophagy

Yamazaki,Kyoka; Hoshi,Masato; Tezuka,Hiroyuki; Morita,Nanaka; Hirayama,Masaya; Sato,Fumiaki; Yoshida,Sayaka; Saito,Kuniaki

doi:10.3892/or.2022.8328

D‑allose enhances the efficacy of hydroxychloroquine against Lewis lung carcinoma cell growth by inducing autophagy

Authors:
- Kyoka Yamazaki
- Masato Hoshi
- Hiroyuki Tezuka
- Nanaka Morita
- Masaya Hirayama
- Fumiaki Sato
- Sayaka Yoshida
- Kuniaki Saito
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Affiliations: Department of Disease Control and Prevention, Fujita Health University, Aichi 470‑1192, Japan, Department of Informative Clinical Medicine, Fujita Health University, Aichi 470‑1192, Japan, Department of Cellular Function Analysis, Research Promotion Headquarters, Fujita Health University, Aichi 470‑1192, Japan, Department of Morphology and Diagnostic Pathology, Fujita Health University, Aichi 470‑1192, Japan
Published online on: May 10, 2022 https://doi.org/10.3892/or.2022.8328
Article Number: 117
Copyright: © Yamazaki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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