2. Academic Validation
  3. Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastoma

Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastoma

  • Cell Death Dis. 2018 Oct 9;9(10):1032. doi: 10.1038/s41419-018-1058-z.
Xiaoxiong Wang 1 2 3,  Chen Shen 1 2 3,  Zhendong Liu 1 2 3,  Fei Peng 1 2 3,  Xin Chen 1 2 3,  Guang Yang 1 2 3,  Daming Zhang 1 2 3,  Zhiqin Yin 1 2 3,  Jichao Ma 4,  Zhixing Zheng 1 2 3,  Boxian Zhao 1 2 3,  Huailei Liu 1 2 3,  Ligang Wang 1 2 3,  Jianing Wu 1 2 3,  Dayong Han 1 2 3,  Kaikai Wang 1 2 3,  Chen Zhong 1 2 3,  Xu Hou 1 2 3,  Wenyang Zhao 1 2 3,  Mengting Shu 1 2 3,  Xinzhuang Wang 1 2 3,  Shiguang Zhao 5 6 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, 150001, Harbin, Heilongjiang Province, People's Republic of China.
  • 2 Institute of Brain Science, Harbin Medical University, No. 23 Youzheng Street, Nangang District, 150001, Harbin, Heilongjiang Province, People's Republic of China.
  • 3 Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, No. 23 Youzheng Street, Nangang District, 150001, Harbin, Heilongjiang Province, People's Republic of China.
  • 4 Department of Pharmacology, The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, College of Pharmacy of Harbin Medical University, No. 157 Baojian Street, Nangang District, 150001, Harbin, Heilongjiang Province, People's Republic of China.
  • 5 Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, 150001, Harbin, Heilongjiang Province, People's Republic of China. guangsz@hotmail.com.
  • 6 Institute of Brain Science, Harbin Medical University, No. 23 Youzheng Street, Nangang District, 150001, Harbin, Heilongjiang Province, People's Republic of China. guangsz@hotmail.com.
  • 7 Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, No. 23 Youzheng Street, Nangang District, 150001, Harbin, Heilongjiang Province, People's Republic of China. guangsz@hotmail.com.
PMID: 30302016 DOI: 10.1038/s41419-018-1058-z
Abstract

Glioblastoma is the most common and aggressive primary brain tumor in adults. New drug design and development is still a major challenge for glioma treatment. Increasing evidence has shown that nitazoxanide, an antiprotozoal drug, has a novel antitumor role in various tumors and exhibits multiple molecular functions, especially autophagic regulation. However, whether nitazoxanide-associated Autophagy has an antineoplastic effect in glioma remains unclear. Here, we aimed to explore the underlying molecular mechanism of nitazoxanide in glioblastoma. Our results showed that nitazoxanide suppressed cell growth and induced cell cycle arrest in glioblastoma by upregulating ING1 expression with a favorable toxicity profile. Nitazoxanide inhibited Autophagy through blockage of late-stage lysosome acidification, resulting in decreased cleavage of ING1. A combination with chloroquine or Torin1 enhanced or impaired the chemotherapeutic effect of nitazoxanide in glioblastoma cells. Taken together, these findings indicate that nitazoxanide as an Autophagy Inhibitor induces cell cycle arrest in glioblastoma via upregulated ING1 due to increased transcription and decreased post-translational degradation by late-stage autophagic inhibition.

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