α-Lipoic acid induces Endoplasmic Reticulum stress-mediated apoptosis in hepatoma cells.
Monica PibiriPia SulasTania CamboniVera Piera LeoniGabriella SimbulaPublished in: Scientific reports (2020)
Hepatocellular carcinoma (HCC) is the most common liver cancer and a major cause of adult death. The current treatments for HCC suffer from drug resistance and poor prognosis; therefore, novel therapeutic agents are urgently needed. Phytochemicals have been proposed to treat a range of cancers. Among them, α-lipoic acid (α-LA), a naturally synthesized antioxidant found in various dietary animal and plant sources, prevents oxidant-mediated cell death in normal cells while inducing apoptosis in several cancer cell lines. Previously, we demonstrated that the treatment of hepatoma cells with α-LA induced apoptosis, which was preceded by the generation of reactive oxygen species (ROS) and activation of the p53 protein, a known inducer of mitochondria-mediated apoptosis. Several studies have shown that ROS-induced apoptosis is associated with endoplasmic reticulum (ER) stress and Unfolded Protein Response (UPR) activation. Herein, we investigated if α-LA-induced apoptosis in hepatoma cell lines was ER stress- and UPR-mediated by gene expression profiling analyses. UPR and ER stress pathways were the most up-regulated after treatment with α-LA. This finding, which has been confirmed by expression analyses of ER- and UPR-associated proteins, provides a better understanding of the molecular mechanisms behind the anti-tumoral action of α-LA on hepatoma cells.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- oxidative stress
- poor prognosis
- signaling pathway
- cell death
- reactive oxygen species
- endoplasmic reticulum
- cell cycle arrest
- dna damage
- squamous cell carcinoma
- genome wide
- dna methylation
- pi k akt
- transcription factor
- high resolution
- anti inflammatory
- mass spectrometry
- papillary thyroid