Scutellarein nanoparticles suppress colon cancer via PHB2-mediated mitophagy inhibition with modulatory effects on tumor-associated depression and osteotropic migration
- 1Department of Anorectal Surgery, Shenzhen TCM Anorectal Hospital (Futian)
Abstract
Background: Colorectal cancer progression involves mitophagy, in which Prohibitin 2 (PHB2) regulates the PARL–PGAM5–PINK1 axis. Scutellarein has antitumor activity but poor bioavailability. We developed integrin αvβ3-targeted β-cyclodextrin-based scutellarein nanoparticles (Scu-NPs), which enhance the solubility, stability, and tumor-targeting of scutellarein, and investigated whether they suppress colon cancer via PHB2-mediated mitophagy inhibition and modulate tumor-associated depression and osteotropic migration.
Methods: PHB2 expression and mitochondrial localization were examined in colon cancer cells. SW480 cells with PHB2 overexpression were treated with Scu or Scu-NPs. Proliferation, migration, invasion, apoptosis, mitochondrial function, and mitophagy-related proteins were assessed. Subcutaneous xenografts, a chronic unpredictable mild stress tumor–depression model, behavioral tests, osteotropic migration assays, and bioinformatics were used.
Results: PHB2 was highly expressed and mitochondria-localized in colon cancer cells. Scu-NPs downregulated PHB2, increased PARL, decreased PGAM5, PINK1, Parkin, and LC3-II/LC3-I, and increased P62, indicating mitophagy inhibition. Scu-NPs induced mitochondrial dysfunction, ROS accumulation, apoptosis, and inhibited proliferation, migration, and invasion; PHB2 overexpression partially reversed these effects. In vivo , Scu-NPs suppressed xenograft growth and improved depressive-like behaviors, with PHB2 overexpression attenuating these effects. In vitro , Scu-NPs reduced colon cancer cell migration toward osteoblast-conditioned medium, whereas PHB2 overexpression partially reversed this effect.
Conclusion: Scu-NPs suppress colon cancer by downregulating PHB2 and inhibiting mitophagy. PHB2 may serve as a shared molecular node linking tumor progression, depressive-like behaviors, and osteotropic migration, supporting Scu-NPs as a multi-target strategy.
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BibTeX
@article{li2026scutellarein,
title = {{Scutellarein nanoparticles suppress colon cancer via PHB2-mediated mitophagy inhibition with modulatory effects on tumor-associated depression and osteotropic migration}},
author = {Yuanzhi Li and Hao Xu and Zonglin Cai and Shimei Liu and Xuqiang Luo and Jinghua Liang and Yingying Liao},
journal = {Frontiers in Public Health},
year = {2026},
month = oct,
doi = {10.3389/fpubh.2026.1996414},
url = {https://www.frontiersin.org/articles/10.3389/fpubh.2026.1996414/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Scutellarein nanoparticles suppress colon cancer via PHB2-mediated mitophagy inhibition with modulatory effects on tumor-associated depression and osteotropic migration
AU - Yuanzhi Li
AU - Hao Xu
AU - Zonglin Cai
AU - Shimei Liu
AU - Xuqiang Luo
AU - Jinghua Liang
AU - Yingying Liao
PY - 2026
DA - 2026/10/28
JO - Frontiers in Public Health
DO - 10.3389/fpubh.2026.1996414
UR - https://www.frontiersin.org/articles/10.3389/fpubh.2026.1996414/full
AB - Background: Colorectal cancer progression involves mitophagy, in which Prohibitin 2 (PHB2) regulates the PARL–PGAM5–PINK1 axis. Scutellarein has antitumor activity but poor bioavailability. We developed integrin αvβ3-targeted β-cyclodextrin-based scutellarein nanoparticles (Scu-NPs), which enhance the solubility, stability, and tumor-targeting of scutellarein, and investigated whether they suppress colon cancer via PHB2-mediated mitophagy inhibition and modulate tumor-associated depression and osteotropic migration. Methods: PHB2 expression and mitochondrial localization were examined in colon cancer cells. SW480 cells with PHB2 overexpression were treated with Scu or Scu-NPs. Proliferation, migration, invasion, apoptosis, mitochondrial function, and mitophagy-related proteins were assessed. Subcutaneous xenografts, a chronic unpredictable mild stress tumor–depression model, behavioral tests, osteotropic migration assays, and bioinformatics were used. Results: PHB2 was highly expressed and mitochondria-localized in colon cancer cells. Scu-NPs downregulated PHB2, increased PARL, decreased PGAM5, PINK1, Parkin, and LC3-II/LC3-I, and increased P62, indicating mitophagy inhibition. Scu-NPs induced mitochondrial dysfunction, ROS accumulation, apoptosis, and inhibited proliferation, migration, and invasion; PHB2 overexpression partially reversed these effects. In vivo , Scu-NPs suppressed xenograft growth and improved depressive-like behaviors, with PHB2 overexpression attenuating these effects. In vitro , Scu-NPs reduced colon cancer cell migration toward osteoblast-conditioned medium, whereas PHB2 overexpression partially reversed this effect. Conclusion: Scu-NPs suppress colon cancer by downregulating PHB2 and inhibiting mitophagy. PHB2 may serve as a shared molecular node linking tumor progression, depressive-like behaviors, and osteotropic migration, supporting Scu-NPs as a multi-target strategy.
SN - 2296-2565
ER -