2. Academic Validation
  3. SBF-1 suppresses colorectal cancer cell growth via modulating cholesterol metabolic reprogramming

SBF-1 suppresses colorectal cancer cell growth via modulating cholesterol metabolic reprogramming

  • Biochem Biophys Res Commun. 2026 Jan 1:794:153046. doi: 10.1016/j.bbrc.2025.153046.
Xuejiao Liang 1,  Liangliang Lu 1,  Ningxin Wang 1,  Biao Yu 2,  Qiang Xu 3,  Qiong Luo 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, China.
  • 2 State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Shanghai, China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, China; Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: [email protected].
  • 4 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, China. Electronic address: [email protected].
PMID: 41317708 DOI: 10.1016/j.bbrc.2025.153046
Abstract

Colorectal Cancer (CRC) is a highly prevalent malignancy globally, ranking among the top three causes of cancer-related deaths, which underscores the urgent need for novel therapeutic approaches. Here, we investigated the antitumor activity and mechanism of SBF-1, a bioactive substance isolated from Ornithogalum caudatum Jacq. SBF-1 significantly inhibited the viability of multiple CRC cell lines by inducing dose-dependent degradation of oxysterol-binding protein (OSBP), leading to reduced intracellular Cholesterol levels. Further investigation demonstrated that SBF-1 reprograms Cholesterol metabolism by suppressing Cholesterol biosynthesis while enhancing efflux and esterification pathways, thereby disrupting cellular Cholesterol homeostasis. Comparative transcriptomic analysis of SW480 and SW620 colorectal Cancer cells identified NPC2 as a key determinant of SBF-1 sensitivity: low NPC2 expression correlated with greater Cholesterol depletion and higher cytotoxicity. Knockdown of NPC2 sensitized resistant cells to SBF-1, whereas NPC2 overexpression conferred resistance. Collectively, our findings reveal that SBF-1 exerts potent cytotoxic effects on colorectal Cancer cells through OSBP degradation-mediated Cholesterol metabolic reprogramming, with NPC2 serving as a critical modulator of cellular susceptibility. This study provides a solid theoretical foundation for the development of novel precision Anticancer therapies targeting Cholesterol metabolism.

Keywords

Cholesterol metabolism; Colorectal cancer; NPC2; OSBP; SBF-1.

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