Research articles
ScienceAsia 50 (2024):ID 2024088 1-9 |doi:
10.2306/scienceasia1513-1874.2024.088
Nobiletin inhibits cell proliferation and invasion via
suppression of UBE2C in hepatocellular carcinoma
Jinzhan Su, Shufeng Fan, Dongying Su, Miaoer Li, Xia Song*
ABSTRACT: Nobiletin is a polymethoxylated flavone derived from Citrus. It is used in traditional Chinese medicine
due to its antitumor activity against a variety of malignant tumors. However, the biological function of nobiletin in
hepatocellular carcinoma (HCC) and its underlying mechanism is largely unknown. The experiments were performed
by treatment of two HCC cell lines (SMMC-7721 and Huh-7) with nobiletin at various concentrations for 48 h. The
results showed that nobiletin possessed cytotoxicity to both HCC cell lines, as determined by MTT assay, in a dosedependent manner. Meanwhile, cell proliferation, migration, and invasion, as assessed by colony formation and
Transwell assays, were inhibited in both cells after being treated with nobiletin. Western blotting was performed
to measure the expression of ubiquitin-conjugating enzyme E2 C (UBE2C), E-cadherin, and N-cadherin. UBE2C
expression was reduced in nobiletin-treated HCC cells, while its expression was increased in HCC tissues and cell lines,
and positively correlated with a shorter survival time of patients with HCC. Mechanistically, nobiletin exhibited antiproliferation and anti-aggressive effects on HCC cells via downregulation of UBE2C. Moreover, nobiletin administration
restricted tumor growth in the HCC xenografts model conducted on nude mice. In conclusion, nobiletin suppressed
proliferation, migration, and invasion of HCC cells by reducing UBE2C, suggesting its potential use as an effective
therapeutic agent for the treatment of HCC.
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Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University,
Zhejiang 310005 China |
* Corresponding author, E-mail: 20084008@zcmu.edu.cn
Received 28 Nov 2023, Accepted 8 Aug 2024
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