Hesperidin enhanced anti-breast cancer effect and alleviated cisplatin induced nephrotoxicity through silk fibroin delivery system

  • Toxicol Appl Pharmacol. 2025 Feb:495:117234. doi: 10.1016/j.taap.2025.117234.
Yonglong Jin  1 ,  Nina Dong  2 ,  Shosei Shimizu  3 ,  Yinuo Li  4 ,  Yuan Yao  5 ,  Hong Qiao  6 ,  Xiguang Liu  2 ,  Shuai Liu  7 ,  Chuanlong Guo  7 ,  Lijie Wang  8
Affiliations
  • 1. Department of Radiotherapy, The Affiliated Hospital of Qingdao University, Qingdao 266000, China; School of Public Health, Qingdao University, Qingdao 266071, China.
  • 2. Department of Radiotherapy, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.
  • 3. Department of Radiotherapy, Yizhou Tumor Hospital, Zhuozhou 072750, China; Department of Radiotherapy, University of Tsukuba Hospital, Tsukuba, Japan.
  • 4. Department of Radiotherapy, University of Tsukuba Hospital, Tsukuba, Japan.
  • 5. Graduate School of Environmental Science, Hokkaido University, Sapporo, Hokkaido, Japan.
  • 6. Hauolilly-MEDICAL company, Tokyo, Japan.
  • 7. Qingdao University of Science and Technology, Qingdao 266041, China.
  • 8. Department of Radiotherapy, The Affiliated Hospital of Qingdao University, Qingdao 266000, China. Electronic address: [email protected].
PMID: 39832567 DOI: 10.1016/j.taap.2025.117234
Abstract

The incidence rate and mortality rate of breast Cancer remain high, and there is an urgent need for safe and effective drugs. The excellent biological activity of hesperidin (HE) is a potential drug for the treatment of breast Cancer. In this study, silk fibroin peptides (SFP) were used as delivery carriers and HE loaded SFP nanofibers (SFP/HE NFs) was prepared. The in vitro results showed that SFP/HE NFs significantly inhibited the proliferation and migration of breast Cancer cell MDA-MB-231 compared with free HE. The mechanism results demonstrated that SFP/HE NFs induced Apoptosis and DNA double stranded damage (DSBs) and further activated the cyclic monophosphate guanosine adenosine monophosphate synthase- stimulator of interferon gene (cGAS-STING) pathway. The in vivo studies showed that SFP/HE NFs treatment significantly inhibited the growth of breast Cancer, with an inhibition rate of 65.9 % (100 mg/kg). In vivo mechanism studies also demonstrated that the anti-tumor activity of SFP/HE NFs was related to the activation of the cGAS-STING pathway. Interestingly, we found that the combination of SFP/HE NFs and cisplatin not only enhanced the anti-tumor activity of cisplatin, but also alleviated cisplatin induced nephrotoxicity. In conclusion, our results demonstrate the benefits of activating the cGAS-STING pathway in the treatment of breast Cancer, which is expected to provide potential candidates for combined treatment of breast Cancer.

Keywords
Breast cancer; Hesperetin; Silk fibroin peptide; cGAS-STING pathway.
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