Abstract
Background
Colorectal cancer (CRC) represents a leading cause of cancer morbidity and mortality globally. Tschimgine (Tsc), a naturally occurring terpenoid from Ferula ovina, has exhibited potent anticancer activity in preclinical models. However, its ability to enhance the sensitivity of CRC cells to 5-Fluorouracil (5-FU) remains unexplored. This study examined the pro-apoptotic and anti-metastatic properties of Tsc, both individually and in combination with 5-FU, in HT-29 human colorectal adenocarcinoma cells.
Methods
HT-29 CRC cells and HFF human fibroblast cells were treated with Tsc, 5-FU, or their combination. Cell viability was assessed using the MTT assay. Apoptotic activity and cell cycle distribution were evaluated through flow cytometry. Migration capacity was tested using a scratch wound healing assay. Expression of apoptosis-related (Bax and Bcl-2) and metastasis-related genes (MMP-2 and MMP-9) was measured by qRT-PCR.
Results
Co-treatment with Tsc and 5-FU demonstrated a synergistic, dose-dependent reduction in HT-29 cell viability with minimal cytotoxicity toward HFF cells. Apoptosis was markedly enhanced in the combination group, evidenced by upregulated Bax and downregulated Bcl-2 expression. The combination also led to marked inhibition of cell migration and downregulation of MMP-2 and MMP-9.
Conclusions
Tsc enhances 5-FU efficiency in inhibiting the growth and metastatic potential of HT-29 colorectal cancer cells. These results show the promising therapeutic effects of the combination of these two drugs, and more studies are needed to confirm their clinical use in the treatment of CRC.
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Abbreviations
- 5-FU:
-
5‑Fluorouracil
- ANOVA:
-
Analysis of variance
- cDNA:
-
Complementary DNA
- CI:
-
Combination index
- CRC:
-
Colorectal cancer
- DMEM:
-
Dulbecco’s Modified Eagle Medium
- DMSO:
-
Dimethyl sulfoxide
- FBS:
-
Fetal bovine serum
- FITC:
-
Fluorescein isothiocyanate
- GH:
-
Gelam honey
- HFF:
-
Human foreskin fibroblasts
- IC₅₀:
-
Half‑maximal inhibitory concentration
- MMPs:
-
Matrix metalloproteinases
- mRNA:
-
Messenger RNA
- PBS:
-
Phosphate‑buffered saline
- PI:
-
Propidium iodide
- qRT‑PCR:
-
Quantitative real‑time PCR
- RNase A:
-
Ribonuclease A
- SD:
-
Standard deviation
- Tsc:
-
Tschimgine
Acknowledgements
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Funding
The authors would like to thank the research council of Birjand University of Medical Sciences for the financial support (Grant Number: 457297).
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Taheri, S., Taghizadeh, B., Rafiei, H. et al. Synergistic effects of Tschimgine combined with 5-Fluorouracil against HT-29 human colorectal cancer cells. BMC Complement Med Ther (2026). https://doi.org/10.1186/s12906-026-05520-1
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DOI: https://doi.org/10.1186/s12906-026-05520-1