Open Access

Fucoxanthin suppresses pancreatic cancer progression by inducing bioenergetics metabolism crisis and promoting SLC31A1‑mediated sensitivity to DDP

  • Authors:
    • Fugen Shangguan
    • Nengfang Ma
    • Yang Chen
    • Yuansi Zheng
    • Ting Ma
    • Jing An
    • Jianhu Lin
    • Hailong Yang
  • View Affiliations

  • Published online on: March 6, 2025     https://doi.org/10.3892/ijo.2025.5737
  • Article Number: 31
  • Copyright: © Shangguan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Pancreatic cancer (PC) is one of the most malignant tumors, with a 5‑year survival rate <10%. Chemosynthetic drugs are widely used in the treatment of PC; however, their toxicity and side effects often reduce the quality of life for patients. MTT and colony formation assay were performed to detect cell growth and viability in PC cells. Levels of ROS in whole cell and mitochondria were analyzed through flow cytometry. ATP production was evaluated using an ATP Assay Kit. Cellular bioenergetics were analyzed with a Seahorse XFe96 Analyzer, and changes in target molecules were monitored by western blotting. The present study reports that fucoxanthin (FX), a carotenoid derived from aquatic brown seaweed, significantly inhibits PC by inhibiting cell proliferation and inducing cell death via the non‑classical pathway. FX switches mitochondrial respiration to aerobic glycolysis in PC cells. Furthermore, FX decreases whole‑cell ATP levels, which indicates that promotion of glycolysis does not compensate for FX‑induced ATP depletion in mitochondria. Moreover, FX decreased the reduced glutathione/oxidized glutathione ratio observed under glucose‑limited conditions. These alterations caused by FX may decrease metabolic flexibility, indicating higher sensitivity to glucose‑limited (GL) conditions. FX increased the cytotoxicity of cisplatin (DDP) and the expression of solute carrier family 31 member 1 (SLC31A1) in PC cells. Furthermore, the knockdown of SLC31A1 can attenuate cytotoxicity caused by the combination of FX and DDP. It was inferred that FX increased the sensitivity of PC cells to DDP), potentially by upregulating SLC31A1 expression. In conclusion, FX exhibited potent antitumor effects by reprogramming energy metabolism and inducing a distinct form of regulated cell death. Therefore, combining FX with GL treatment or DDP presents a promising therapeutic strategy for PC.
View Figures
View References

Related Articles

Journal Cover

April-2025
Volume 66 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Shangguan F, Ma N, Chen Y, Zheng Y, Ma T, An J, Lin J and Yang H: Fucoxanthin suppresses pancreatic cancer progression by inducing bioenergetics metabolism crisis and promoting SLC31A1‑mediated sensitivity to DDP. Int J Oncol 66: 31, 2025.
APA
Shangguan, F., Ma, N., Chen, Y., Zheng, Y., Ma, T., An, J. ... Yang, H. (2025). Fucoxanthin suppresses pancreatic cancer progression by inducing bioenergetics metabolism crisis and promoting SLC31A1‑mediated sensitivity to DDP. International Journal of Oncology, 66, 31. https://doi.org/10.3892/ijo.2025.5737
MLA
Shangguan, F., Ma, N., Chen, Y., Zheng, Y., Ma, T., An, J., Lin, J., Yang, H."Fucoxanthin suppresses pancreatic cancer progression by inducing bioenergetics metabolism crisis and promoting SLC31A1‑mediated sensitivity to DDP". International Journal of Oncology 66.4 (2025): 31.
Chicago
Shangguan, F., Ma, N., Chen, Y., Zheng, Y., Ma, T., An, J., Lin, J., Yang, H."Fucoxanthin suppresses pancreatic cancer progression by inducing bioenergetics metabolism crisis and promoting SLC31A1‑mediated sensitivity to DDP". International Journal of Oncology 66, no. 4 (2025): 31. https://doi.org/10.3892/ijo.2025.5737