Published online Dec 20, 2025. doi: 10.5493/wjem.v15.i4.110757
Revised: July 12, 2025
Accepted: November 3, 2025
Published online: December 20, 2025
Processing time: 188 Days and 6.2 Hours
Colon cancer is a major health problem with increasing mortality rates world
To evaluate the ability of Ferula assafoetida (F. assafoetida) to induce differentiation of colon cancer cells to function as normal cells.
The cytotoxic effect of F. assafoetida was assessed against Caco cells using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphe nyltetrazoliumbromide thiazolyl assay. Cell cycle analysis and apoptosis were assessed using CytellTM cell system. The total antioxidant (TA), glutathione (GSH), malondialdehyde (MDA) concentrations, and alkaline phosphatase (ALP) activity were also assessed. The c-Jun N-terminal kinases (JNKs) and mitogen-activated protein kinase (MAPK) expressions were evaluated using quantitative real-time polymerase chain reaction.
There was a significant increase in the cell number treated with F. assafoetida (53.85% ± 0.03%), and those treated with sodium butyrate (NaBT) (54.6% ± 0.10%) in sub-G1 phase, compared to the untreated cells (0.78% ± 0.03%, P < 0.001). Apoptosis was significantly increased in the Caco cells treated with F. assafoetida (49.1% ± 0.14%) compared to those treated with NaBT (27.3% ± 0.10%, P < 0.001), and untreated cells (11.1% ± 0.02%, P < 0.001). DNA degradation was observed in Caco cells treated with F. assafoetida in a dose-dependent manner, where complete degradation occurred at the dose of IC50 (342.9 μg/mL). F. assafoetida induced a significant increase in the TA concentration and GSH, while a significant decrease in the MDA levels (P < 0.001, for all). Also, there was a significant increase in ALP activity in Caco cells (0.53 ± 0.26 U/mL) compared to the control cells (0.05 ± 0.02 U/mL, P = 0.045). There was a significant upregulation of JNK and MAPK expression in Caco cells treated with F. assafoetida compared to the controls [2.59 ± 0.01 (P < 0.001), and 3.62 ± 0.01 (P < 0.001); respectively].
F. assafoetida is a potentially successful therapeutic and differentiating agent for colon cancer.
Core Tip: Ferula assafoetida (F. assafoetida) could be considered a potential differentiating agent for colon cancer cells through increasing the alkaline phosphatase activity, as well as upregulation of JNK and MAPK gene expression. Additionally, it has important implications for cancer therapy through arresting cells in the sub-G1 phase, inducing cytotoxicity, DNA fragmentation, and apoptosis in the cancer cells compared to those treated with sodium butyrate (NaBT), and untreated control cells. Moreover, F. assafoetida has a protective impact against the cellular oxidative stress revealed by the significant increase in the total antioxidant concentration and glutathione level, while a significant decrease in the malondialdehyde levels in the Caco cells compared to cells treated with NaBT, and the untreated control cells. F. assafoetida is a useful, efficient, inexpensive, and novel therapeutic medicinal herps for colon cancer patients.