Infectious Agents and Cancer (Apr 2023)

Brassicasterol inhibits hepatitis B virus-associated hepatocellular carcinoma development via suppression of AKT signaling pathway

  • Jindi Zeng,
  • Jiancheng Wu,
  • Shuijiao Pang,
  • Feifei Wang,
  • Xin Yu,
  • Shouhua Zhang,
  • Junquan Zeng,
  • Jinlong Yan,
  • Jianping Lian

DOI
https://doi.org/10.1186/s13027-023-00502-1
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 9

Abstract

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Abstract Background Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) does not respond well to current treatment options like sorafenib, and there is an urgent need for developing therapeutical strategies for HBV + HCC. Brassicasterol has previously shown anti-cancer and anti-viral activities, however, its value against HBV + HCC remains to be explored. Methods The inhibitory effect of brassicasterol and sorafenib was evaluated on HBV + HCC cell lines and xenograft mouse model. The cytotoxicity of brassicasterol on normal liver cells were measured by LDH assay. AKT agonist was used to identify the targeted signaling pathway by brassicasterol. Results Brassicasterol induced HBV + HCC cell death in a both dose-dependent and time-dependent manner, and such inhibition was more potent than sorafenib. Brassicasterol did not show apparent cytotoxicity to normal liver cells. Xenograft mouse model further confirmed the inhibitory effect of brassicasterol on the growth of HBV + HCC. Furthermore, signaling pathway analysis showed that brassicasterol-treated HBV + HCC cells had decreased level of phosphor-AKT expression while the addition of AKT agonist could counteract the inhibitory effect of brassicasterol on HCC, indicating that brassicasterol suppressed AKT pathway to exhibit anti-cancer activity in HBV + HCC cells. In addition, brassicasterol showed similar levels of inhibition on HBV− and HBV + HCC cells. Conclusion Brassicasterol possesses anti-cancer activity against HCC through the downregulation of AKT pathway and such activity is independent of HBV infection.

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