Evaluation of the Effectiveness of Various Autophagy Inhibitors in A549 Cancer Stem Cells

by Selleckchem | Jul 07 2023

Numerous studies have already established that autophagy plays a central role in the survival of all cells, including malignant ones. Autophagy is a central cog in the general mechanism that provides the intracellular proteostasis determining cellular physiological and phenotypic characteristics. The accumulated data show that autophagy largely contributes to cancer cell stemness. Thus, autophagy modulation is considered one of the promising pharmacological targets in therapy aimed at cancer stem cell elimination. However, autophagy is a multi-stage intracellular process that involves numerous protein participants. In addition, the process can be activated simultaneously by various signaling modules. Therefore, it is no small feat to select an effective pharmacological drug against autophagy. What's more, the search for potential chemotherapeutic agents that could eliminate cancer stem cells through pharmacological inhibition of autophagy is still under way. In the present work, we selected a panel of autophagy inhibitors (Autophinib, SBI-0206965, Siramesine, MRT68921, and IITZ-01), some of whom have been recently identified as effective autophagy inhibitors in cancer cells. Using A549 cancer cells, which express the core stem factors Oct4 and Sox2, we evaluated the effect of these drugs on the survival and preservation of the original properties of cancer stem cells. Among the agents selected, only Autophinib demonstrated a significant toxic effect on cancer stem cells. The obtained results demonstrate that autophagy inhibition by Autophinib downregulates the expression of the Sox2 protein in A549 cells, and that this downregulation correlates with a pronounced induction of apoptosis. Moreover, Autophinib-treated A549 cells are unable to form spheroids, which indicates a reduction in stemness. Thus, among the drugs studied, only Autophinib can be considered a potential agent against cancer stem cells.

Comments:

The paragraph you provided discusses the role of autophagy in cancer cells and its potential as a target for cancer stem cell elimination. It mentions that autophagy modulation is being explored as a promising therapeutic approach, but selecting an effective pharmacological drug against autophagy is a challenging task due to the complexity of the process and the multiple signaling modules involved. The paragraph then describes a study conducted using a panel of autophagy inhibitors (Autophinib, SBI-0206965, Siramesine, MRT68921, and IITZ-01) to evaluate their effects on the survival and properties of cancer stem cells.

The study used A549 cancer cells, which express the stem factors Oct4 and Sox2. Among the autophagy inhibitors tested, only Autophinib demonstrated a significant toxic effect on cancer stem cells. Inhibition of autophagy by Autophinib led to downregulation of Sox2 protein expression in A549 cells, which was associated with an induction of apoptosis (programmed cell death). Additionally, Autophinib-treated A549 cells were unable to form spheroids, indicating a reduction in stemness, a characteristic property of cancer stem cells.

Based on these findings, the study suggests that Autophinib may be a potential agent for targeting cancer stem cells through autophagy inhibition. It implies that Autophinib's ability to downregulate Sox2 expression and induce apoptosis, as well as its impact on stemness, make it a promising candidate for further exploration in the development of chemotherapeutic agents aimed at eliminating cancer stem cells.

It's important to note that the information provided is based on the paragraph you provided, and I don't have access to the full details of the study or additional context.