2. Academic Validation
  3. Vitamin D3 suppresses the cholesterol homeostasis pathway in patient-derived glioma cell lines

Vitamin D3 suppresses the cholesterol homeostasis pathway in patient-derived glioma cell lines

  • FEBS Open Bio. 2023 Jul 25. doi: 10.1002/2211-5463.13679.
Ran Yuan 1 2 3,  Wei Zhang 4 5 6,  Yong-Ping You 7,  Gang Cui 8,  Zhengliang Gao 9 10,  Xiuxing Wang 11,  Jian Chen 1 2 3
Affiliations

Affiliations

  • 1 Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, China.
  • 2 Chinese Institute for Brain Research, Beijing, China.
  • 3 Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing, China.
  • 4 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  • 5 China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  • 6 Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
  • 7 Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, China.
  • 8 Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • 9 Fundamental Research Center, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China.
  • 10 Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, China.
  • 11 National Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, China.
PMID: 37489660 DOI: 10.1002/2211-5463.13679
Abstract

Glioblastoma is one of the most common malignant brain tumors. Vitamin D, primarily its hormonally active form calcitriol, has been reported to have anti-cancer activity. In the present study, we used patient-derived glioma cell lines to examine the effect of vitamin D3 and calcitriol on glioblastoma. Surprisingly, vitamin D3 showed a more significant inhibitory effect than calcitriol on cell viability and proliferation. Vitamin D receptor (VDR) mediates most of the cellular effects of vitamin D, and thus we examined the expression level and function of VDR via gene silencing and gene knockout experiments. We observed that VDR does not affect the sensitivity of patient-derived glioma cell lines to vitamin D3, and the gene encoding VDR is not essential for growth of patient-derived glioma cell lines. RNA sequencing data analysis and sterolomics analysis revealed that vitamin D3 inhibits Cholesterol synthesis and Cholesterol homeostasis by inhibiting the expression level of 7-dehydrocholesterol reductase, which leads to the accumulation of 7-dehydrocholesterol and other sterol intermediates. In conclusion, our results suggest that vitamin D3, rather than calcitriol, inhibits growth of patient-derived glioma cell lines via inhibition of the Cholesterol homeostasis pathway.

Keywords

calcitriol; cholesterol homeostasis; glioblastoma; vitamin D receptor; vitamin D3.

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