2-Methyl 2-butanol suppresses human retinoblastoma cells through cell cycle arrest and autophagy

Abstract

2-Methyl-2-butanol (MBT) is a chemical compound from the group of alcohols more specifically pentanols, which has shown an excellent anti-cancer activity in our previous study. However, its mechanism of action remains unclear. The present study was designed to investigate the anti-cancer effect of MBT on human retinoblastoma cells. The results showed that the use of MBT leads to HXO-RB44 cell death but is cytotoxic to normal cells at higher concentrations. It showed a dose- as well as a time-dependent inhibition of HXO-RB44 cells. P27 is a cell cycle inhibitory protein, which plays an important role in cell cycle regulation whereas cyclin-B1 is a regulatory protein involved in mitosis. MBT increased the cell cycle arrest in a dose-dependent manner by augmenting p27 and reducing cyclin B1 expression. Moreover, it also accelerated apoptosis, increased light chain-3 (LC-3) conversion in a dose-dependent manner, and helped to debulk cancerous cells. LC3 is a soluble protein, which helps to engulf cytoplasmic components, including cytosolic proteins and organelles during autophagy from autophagosomes. In order to verify the effect of MBT, bafilomycin A1, an autophagy inhibitor, was used to block the MTB-induced apoptosis and necrosis. Additionally, a specific Akt agonist, SC-79, reversed the MBT-induced cell cycle arrest and autophagy. Thus, from the present study, it was concluded that MBT induced cell cycle arrest, apoptosis and autophagy through the PI3K/Akt pathway in HXO-RB44 cells.

Advances in the role of autophagy in the development of retinoblastoma (Review)

“…On the contrary, the aforementioned drugs with anti-RB effects may induce autophagy and lead to important drug resistance, similar to numerous anti-RB drugs such as etoposide and cisplatin. A number of studies reached the opposite conclusion, and found that dimethyldibutanol 2-methyl-2-butanol (MBT) led to RB cell apoptosis, while the use of autophagy inhibitors blocked the action of this drug (69). These results indicate that the anti-RB effect of MBT may be associated with an increase in the autophagy level, while the specific mechanism remains unknown.…”