We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Delta-tocotrienol enhances the anti-tumor effects of interferon alpha through reactive oxygen species and Erk/MAPK signaling pathways in hepatocellular carcinoma cells.
- Authors
Lucci, Alvaro; Vera, Marina C.; Comanzo, Carla G.; Lorenzetti, Florencia; Ferretti, Anabela C.; Ceballos, María Paula; Quiroga, Ariel D.; Alvarez, María de Luján; Carrillo, María Cristina
- Abstract
The complexity of hepatocellular carcinoma (HCC) signaling and the failure of pharmacological therapeutics reveal the significance of establishing new anti-cancer strategies. Interferon alpha (IFN-α) has been used as adjuvant therapy for reducing HCC recurrence and improving survival. Delta-tocotrienol (δ-tocotrienol), a natural unsaturated isoform of vitamin E, is a promising candidate for cancer treatment. In this study, we evaluated whether the combination of δ-tocotrienol with IFN-α displays significant advantages in the treatment of HCC cells. Results showed that the combination significantly decreased cell viability, migration and invasion of HCC cells compared with single therapies. Combining δ-tocotrienol and IFN-α enhanced the decrease in proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase (MMP) 7 and MMP-9. The combination also produced an enhancement of apoptosis together with increased Bax/Bcl-xL ratio and reactive oxygen species (ROS) generation. δ-tocotrienol induced Notch1 activation and changes in Erk and p38 MAPK signaling status. Blocking experiments confirmed that ROS and Erk are involved, at least in part, in the anti-cancer effects of the combined treatment. In conclusion, the combination of δ-tocotrienol with IFN-α therapy showed promising results for HCC cell treatment, which makes the combination of cytokine-based immunotherapy with natural products a potential strategy against liver cancer.
- Subjects
REACTIVE oxygen species; INTERFERON alpha; HEPATOCELLULAR carcinoma; PROLIFERATING cell nuclear antigen; MITOGEN-activated protein kinases; INTERFERON beta 1b; TYPE I interferons; EXTRACELLULAR signal-regulated kinases
- Publication
Canadian Journal of Physiology & Pharmacology, 2022, Vol 100, Issue 5, p453
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2021-0606