The Role of Metformin on the Expression of Apoptosis-Related Caspase Family Members

Abstract

Metformin is the main line drug in the treatment of type 2 diabetes mellitus. However, now metformin has
been widely studied for its potential for the treatment of various diseases. Apoptosis is a programmed
cell death mechanism mediated by various proteins from the caspase family. Furthermore, the apoptotic
caspases are subdivided into the initiators (caspase-2, -8, -9, and -10) and the effectors (caspase-3, -6,
and -7). Various studies have reported that metformin could induce apoptosis, while other studies have
reported otherwise. This study aimed to reveal the role of metformin on the expression of caspase
proteins associated with apoptosis. Bioinformatics analysis using STITCH v.5.0 was performed to predict
the metformin-caspase interactions. The results showed that metformin could directly activate caspase3 and -7. However, at the same time, metformin could also inhibit the expression of caspase-3 and -8.
Furthermore, metformin did not interact directly with caspases -2, -6, -9, and -10. Through this study, it
can be concluded that metformin has dual roles (activation and inhibition) in the expression of apoptosisrelated caspase proteins.