Ion transport across the cell membranes is facilitated by a certain class of membrane proteins known as ion channels and transporters. Concentration of ions within cells is prone to changes as the external environment varies. But cells have a built-in mechanism, called homeostasis, to maintain optimal levels of ions.
Disruption in ion homeostasis, as can happen in the case of mutations in natural ion channels, can lead to disease conditions. Synthetic ion transport systems have shown promise in ion channel replacement therapy while also serving as useful tools to study transmembrane ion transport processes.
Considering that impaired regulation of ion homeostasis leads to apoptosis or programmed cell death (PCD), researchers at IISER Pune chose to address how chloride ion-signaling pathways could serve as targets for anticancer drugs.
Research group of Pinaki Talukdar with PhD student Tanmoy Saha and that of Mayurika Lahiri have developed a synthetic organic molecule, bis(sulfonamide) compound, which selectively binds to and transports chloride ions across the phospholipid bilayer.
In their recent report in the Journal of the American Chemical Society, the team has shown that delivery of chloride ions mediated by the bis(sulfonamide) compound leads to disruption of chloride ion homeostasis of cells and activates apoptosis, a process of programmed cell death (PCD). By monitoring various cellular parameters such as the change in mitochondrial membrane potential, cytochrome c leakage, activation of family of caspases, and nuclear fragmentation, the team has established that cell death is mediated by the newly developed chloride ion delivery system.
Inactivation of PCD is crucial to the development of cancer, and tumor cells occasionally develop resistance to the common cancer treatment regimens by disabling of apoptotic pathways. Talukdar and Lahiri envisage that the synthetic transmembrane chloride ion transporters may offer a new therapeutic tool for cancer treatment in the next generation by reactivating this disabled process.
The paper titled “Chloride-mediated apoptosis-inducing activity of bis(sulfonamide) anionophores” and authored by Tanmoy Saha, Munshi Sahid Hossain, Debasis Saha, Mayurika Lahiri, and Pinaki Talukdar has been published the Journal of the American Chemical Society (138(24):7558-7567).
This work received funding from SERB India.