Mechanism of Curcumol Targeting the OTUB1/TGFBI Ubiquitination Pathway in the Inhibition of Angiogenesis in Colon Cancer

  • Int J Mol Sci. 2025 May 21;26(10):4899. doi: 10.3390/ijms26104899.
Yimiao Zhu  1 ,  Wenya Wu  1 ,  Dahai Hou  2 ,  Yu Zhao  1 ,  Jinshu Ye  1 ,  Lizong Shen  1  3 ,  Tong Zhao  2 ,  Xiaoyu Wu  1
Affiliations
  • 1. First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210046, China.
  • 2. School of Integrated Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 3. Nanjing Medical University, Nanjing 211166, China.
PMID: 40430059 DOI: 10.3390/ijms26104899
Abstract

Tumor angiogenesis and metastasis are critical processes in the progression of colon carcinoma. Curcumol, a bioactive sesquiterpenoid derived from curcuma, exhibits anti-angiogenic properties, though its underlying mechanisms remain unclear. In this study, an HT-29 xenograft mouse model demonstrated that curcumol combined with oxaliplatin significantly suppressed tumor growth (Ki67↓) and microvessel density (CD31↓). In vitro assays revealed that curcumol dose dependently inhibited proliferation (MTT), migration (Transwell), and tube formation (CAM assay) in Caco-2/HT-29 and HUVEC cells. Mechanistically, curcumol downregulated OTUB1 expression, promoting TGFB1 degradation via the ubiquitin-proteasome pathway. OTUB1 overexpression activated the TGFB1/VEGF axis, enhancing cell invasiveness and angiogenesis-effects reversed by high-dose curcumol. These findings identify the OTUB1-TGFB1/VEGF axis as a key target of curcumol in inhibiting colon Cancer angiogenesis, elucidating its anti-tumor mechanism and offering a novel therapeutic strategy for targeted treatment.

Keywords
OTUB1; TGFBI; angiogenesis; colon cancer; curcumol.
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