Esterase‐Activatable Synthetic M⁺/Cl⁻ Channel Induces Apoptosis and Disrupts Autophagy in Cancer Cells

Abstract

The formation of a supramolecular synthetic M+/Cl− channel in the membrane phospholipid bilayer has been reported upon activation of a methyl pivalate‐linked N1,N3‐dialkyl‐2‐hydroxyisophthalamide by esterases. The channel formation induces apoptosis in cancer cells via the intrinsic pathway. Interestingly, the supramolecular channel was also shown to disrupt autophagy in cancer cells by causing alkalization of lysosomes – a feature that has been confirmed at the cellular and protein level.

Molecular Self‐Assembly as a Tool to Construct Transmembrane Supramolecular Ion Channels

“…Therefore, the effect of compound 18 on autophagy was probed using immunoblot analysis which showed decreased expression of Lamin B1 (Figure 17H) and overexpression of LC3 (Figure 17I) compared to GAPDH as a loading control (Figure 17J). These studies suggest the activation of the autophagy process upon treatment with compound 18 [41] …”

Recent Advances in Bioactive Artificial Ionophores

“…This ion channel 71 triggered ion transport across lipid membrane by M + /Cl À symport mechanism. [70] Interestingly, this system induced cancer cell death not only by apoptosis (following an intrinsic pathway), but also by autophagy disruption in MCF 7 cells (Figure 20B).…”

Most recent advances on enzyme‐activatable optical probes for bioimaging

“…Considering this, it is extremely demanding to develop a reliable assay approach for quantifying the esterase activity as well as analyzing cellular status. In the past 2 years, several activatable probes for esterase have been explored [68][69][70][71][72][73][74] and used for the esterase-related applications, such as discriminating live and dead cells, [69] esterase-triggered PDT, [70] and FL imaging of esterase-based biomarker, [74] etc. The representatives are exhibited in Figure 9.…”