1. Academic Validation
  2. Novel SREBP1 inhibitor cinobufotalin suppresses proliferation of hepatocellular carcinoma by targeting lipogenesis

Novel SREBP1 inhibitor cinobufotalin suppresses proliferation of hepatocellular carcinoma by targeting lipogenesis

  • Eur J Pharmacol. 2021 Sep 5;906:174280. doi: 10.1016/j.ejphar.2021.174280.
Huannan Meng 1 Mengqin Shen 2 Jiajin Li 2 Ruixue Zhang 2 Xi Li 3 Li Zhao 2 Gang Huang 4 Jianjun Liu 5
Affiliations

Affiliations

  • 1 Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory for Molecular Imaging, Collaborative Scientific Research Center, Shanghai University of Medicine & Health Science, Shanghai, 200093, China.
  • 2 Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai, 200127, China.
  • 3 Department of Medicinal Material, Changhai Hospital of Shanghai, 200433, China.
  • 4 Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory for Molecular Imaging, Collaborative Scientific Research Center, Shanghai University of Medicine & Health Science, Shanghai, 200093, China; Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • 5 Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory for Molecular Imaging, Collaborative Scientific Research Center, Shanghai University of Medicine & Health Science, Shanghai, 200093, China; Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai, 200127, China. Electronic address: [email protected].
Abstract

Hepatocellular carcinoma (HCC) is the major type of primary liver Cancer and a leading cause of cancer-related deaths worldwide. Cinobufotalin (CBF) is extracted from the skin secretion of the giant toad and clinically used for the treatment of liver Cancer, but its molecular mechanism of anti-cancer in HCC has not yet been elucidated. Here, we showed CBF effectively promoted cell Apoptosis, induced cell cycle G2-M arrest, inhibited cell proliferation and lipogenesis. Consistently, the lipogenesis ability of xenograft examined by 11C-acetate micro-PET/CT imaging, and the tumor growth rate was notably declined in a centration-dependent manner. The fatty acid profiles showed saturated and mono-unsaturated fatty acid significantly decreased after CBF treatment. Mechanistically, CBF selectively inhibited the expression of SREBP1 and interacted with SREBP1 to prevent it from sterol regulatory elements (SREs), thus inhibiting the expression of lipogenic enzymes. Collectively, our study demonstrates that CBF is a potent native compound that remarkably inhibits HCC lipogenesis and tumorigenesis. CBF may possess this therapeutic potential though interfering with de novo lipid synthesis via SREBP1.

Keywords

CBF; Hepatocellular carcinoma; Lipogenesis; SREBP1.

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