According to the research study, the researchers have describing a new mechanisms; which inducing the self-killing of cancer cells by perturbing ion homeostasis. By this the study developing an helical polypeptide potassium ionophores; that lead to the onset of programmed cell death. The ionophores increase the active oxygen concentration to stress endoplasmic reticulum to the point of cellular death.
But the electrochemical gradient between extracellular and intracellular conditions; which playing an important role in cell growth and metabolism. When a cell’s ion homeostasis is disturbing; critical functions accelerating the activation of apoptosis are inhibited in the cell. Although ionophores have been intensively used as an ion homeostasis disturber; the mechanisms of cell death have been unclear and the bio-applicability has been limited.
In the study featured at advanced science; the team presenting an alpha helical peptide-based anticancer agent; that is capable of transporting potassium ions with water solubility. The cationic, hydrophilic, and potassium ionic groups; that were combining at the end of the peptide side chain to provide both ion transport and hydrophilic properties.
Cancer cells by perturbing ion
These peptide-based ionophores reduce the intracellular potassium concentration and at the same time increase the intracellular calcium concentration. Increased intracellular calcium concentrations produce intracellular reactive oxygen species, causing endoplasmic reticulum stress, and ultimately leading to apoptosis. Anticancer effects were evaluating using tumor-bearing mice to confirm the therapeutic effect, even in animal models.
It was finding that tumor growth was strongly inhibiting by endoplasmic stress-mediating apoptosis. A peptide-based ionophore is more effective than conventional chemotherapeutic agents because it induces apoptosis via elevated reactive oxygen species levels. But the study expecting that this new mechanism to be widely using as a new chemotherapeutic strategy.
Mechanisms of cell death
Although ionophores have being intensively usingd as an ion homeostasis disturber; the mechanisms of cell death are unclear and the bioapplicability is limiting. In this study, helical polypeptide‐basing potassium ionophores are developing to induce endoplasmic reticulum (ER) stress‐mediating apoptosis. The polypeptide‐based potassium ionophores disturb ion homeostasis; and then induce prolonged ER stress in the cells.
The ER stress results in oxidative environments that accelerate the activation of mitochondria‐dependent apoptosis. Moreover, ER stress‐mediating apoptosis is triggering in a tumor‐bearing mouse model that suppresses tumor proliferation. This study provides the first evidence showing that helical polypeptide‐based potassium ionophores trigger ER stress‐mediated apoptosis by perturbation of potassium homeostasis.