Tempol Induces Oxidative Stress, ER Stress and Apoptosis via MAPK/Akt/mTOR Pathway Suppression in HT29 (Colon) and CRL-1739 (Gastric) Cancer Cell Lines
Tempol is a synthetic antioxidant that shows promise in preclinical cancer studies by inhibiting growth and inducing apoptosis. Given that the Mitogen-Activated Protein Kinase (MAPK) and Protein Kinase B/Mammalian Target of Rapamycin (Akt/mTOR) signaling pathways are frequently dysregulated in gastr...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/47/7/574 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Tempol is a synthetic antioxidant that shows promise in preclinical cancer studies by inhibiting growth and inducing apoptosis. Given that the Mitogen-Activated Protein Kinase (MAPK) and Protein Kinase B/Mammalian Target of Rapamycin (Akt/mTOR) signaling pathways are frequently dysregulated in gastric and colon cancers and contribute to their progression, we investigated Tempol’s anti-cancer potential in HT29 (colon) and CRL-1739 (gastric) cancer cells. Cells were treated with 2 mM Tempol for 48 h, with untreated cells as controls. We evaluated apoptosis (Bax, cleaved caspase-3, and Bcl-2), key signaling pathway activity (<i>p</i>-ERK, <i>p</i>-JNK, <i>p</i>-AKT, and <i>p</i>-mTOR), and levels of stress- and apoptosis-related proteins (WEE1, GADD153, GRP78, and AIF). Tempol significantly increased pro-apoptotic Bax and cleaved caspase-3 (<i>p</i> < 0.0001) and decreased anti-apoptotic Bcl-2 (<i>p</i> < 0.0001) in both cell lines. Furthermore, Tempol markedly reduced the activity of <i>p</i>-ERK, <i>p</i>-JNK, <i>p</i>-AKT, and <i>p</i>-mTOR (<i>p</i> < 0.0001) and significantly increased the protein levels of WEE1, GADD153, GRP78, and AIF (<i>p</i> < 0.0001). Tempol treatment also led to a significant increase in total oxidant status and a decrease in total antioxidant status. In conclusion, our findings suggest that Tempol exhibits its anti-cancer activity through multiple interconnected mechanisms, primarily inducing apoptosis and oxidative stress, while concurrently suppressing pro-survival signaling pathways. These results highlight Tempol’s potential as a therapeutic agent for gastric and colon cancers. |
|---|---|
| ISSN: | 1467-3037 1467-3045 |