Title:Crocetin Enhances Temozolomide Efficacy in Glioblastoma Therapy Through Multiple Pathway Suppression
Volume: 21
Issue: 3
Author(s): Wei-En Tsai, Yen-Tsen Liu, Fu-Hsuan Kuo, Wen-Yu Cheng, Chiung-Chyi Shen, Ming-Tsang Chiao, Yu-Fen Huang, Yea-Jiuen Liang, Yi-Chin Yang, Wan-Yu Hsieh, Jun-Peng Chen, Szu-Yuan Liu and Cheng-Di Chiu*
Affiliation:
- Spine Center, China Medical University Hospital, Taichung, Taiwan
- Department of Neurosurgery,
China Medical University Hospital, Taichung, Taiwan
Keywords:
Crocetin, glioblastoma, temozolomide, AKT signaling, cell migration, tumor growth.
Abstract:
Background: Glioblastoma multiforme (GBM) is an aggressive type of brain
tumor that is difficult to remove surgically. Research suggests that substances from saffron,
namely crocetin and crocin, could be effective natural treatments, showing abilities to kill cancer
cells.
Methods: Our study focused on evaluating the effects of crocetin on glioma using the U87 cell
line. We specifically investigated how crocetin affects the survival, growth, and spread of glioma
cells, exploring its impact at concentrations ranging from 75-150 μM. The study also included
experiments combining crocetin with the chemotherapy drug Temozolomide (TMZ) to assess
potential synergistic effects.
Results: Crocetin significantly reduced the viability, proliferation, and migration of glioma cells.
It achieved these effects by decreasing the levels of Matrix Metallopeptidase 9 (MMP-9) and
Ras homolog family member A (RhoA), proteins that are critical for cancer progression. Additionally,
crocetin inhibited the formation of cellular structures necessary for tumor growth. It
blocked multiple points of the Ak Strain Transforming (AKT) signaling pathway, which is vital
for cancer cell survival. This treatment led to increased cell death and disrupted the cell cycle in
the glioma cells. When used in combination with TMZ, crocetin not only enhanced the reduction
of cancer cell growth but also promoted cell death and reduced cell replication. This combination
therapy further decreased levels of high mobility group box 1 (HMGB1) and Receptor for
Advanced Glycation End-products (RAGE), proteins linked to inflammation and tumor progression.
It selectively inhibited certain pathways involved in the cellular stress response without
affecting others.
Conclusion: Our results underscore the potential of crocetin as a treatment for glioma. It targets
various mechanisms involved in tumor growth and spread, offering multiple avenues for
therapy. Further studies are essential to fully understand and utilize crocetin’s benefits in treating
glioma.
