ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells

6533b872fe1ef96bd12d3825

RESEARCH PRODUCT

ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells

Daniela Carlisi Anna De Blasio Claudia Pellerito Giuseppe Calvaruso Marianna Lauricella Adriana Celesia Michela Giuliano Sonia Emanuele Antonella D’anneo Ornella Morana Tiziana Fiore

subject

Programmed cell death NF-E2-Related Factor 2 Glucose-regulated protein Apoptosis medicine.disease_cause Article Catalysis Inorganic Chemistry lcsh:Chemistry Settore BIO/10 - Biochimica Autophagy Tumor Cells Cultured medicine Humans Gene silencing oxidative stress Physical and Theoretical Chemistry Endoplasmic Reticulum Chaperone BiP Molecular Biology lcsh:QH301-705.5 tributyltin (IV) derivative Spectroscopy Cell Proliferation oxidative stre biology Chemistry Endoplasmic reticulum Organic Chemistry Autophagy Cancer ROS General Medicine endoplasmic reticulum stre medicine.disease Computer Science Applications Gene Expression Regulation Neoplastic lcsh:Biology (General)lcsh:QD1-999 autophagic cell death Colonic Neoplasms Unfolded protein response Cancer research biology.protein endoplasmic reticulum stress Trialkyltin Compounds Reactive Oxygen Species Oxidative stress

description

Organotin compounds represent potential cancer therapeutics due to their pro-apoptotic action. We recently synthesized the novel organotin ferulic acid derivative tributyltin (IV) ferulate (TBT-F) and demonstrated that it displays anti-tumor properties in colon cancer cells related with autophagic cell death. The purpose of the present study was to elucidate the mechanism of TBT-F action in colon cancer cells. We specifically show that TBT-F-dependent autophagy is determined by a rapid generation of reactive oxygen species (ROS) and correlated with endoplasmic reticulum (ER) stress. TBT-F evoked nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant response and Nrf2 silencing by RNA interference markedly increased the anti-tumor efficacy of the compound. Moreover, as a consequence of ROS production, TBT-F increased the levels of glucose regulated protein 78 (Grp78) and C/EBP homologous protein (CHOP), two ER stress markers. Interestingly, Grp78 silencing produced significant decreasing effects on the levels of the autophagic proteins p62 and LC3-II, while only p62 decreased in CHOP-silenced cells. Taken together, these results indicate that ROS-dependent ER stress and autophagy play a major role in the TBT-F action mechanism in colon cancer cells and open a new perspective to consider the compound as a potential candidate for colon cancer treatment.

year	journal	country	edition	language
2020-10-30

10.3390/ijms21218135 http://hdl.handle.net/10447/445552