IKK16 and SGI1027 induce cytoplasmic vacuolization, and their combination with chemotherapy drugs can enhance the efficacy of cancer therapeutics
TL;DR
It is shown that combining paraptosis-inducing compounds with anti-cancer drugs can reduce the required overall dosage concentration while preserving therapeutic efficacy, potentially revolutionizing cancer treatment.
Abstract
Cell death represents a critical process in the maintenance of cellular homeostasis. Paraptosis, a mechanism of programmed cell death, is distinguished by extensive cytoplasmic vacuolization. We have identified two commercially available compounds, IKK16 and SGI1027, which can induce cytoplasmic vacuolization leading to paraptosis in cancer cells. We have characterized and studied various cancer cell lines by applying molecular biology, proteomics, gene expression analyses, and microscopy-based techniques. Additionally, our gene expression analyses indicate that GADD45A, and NPC2 genes may serve as potential markers for identifying paraptosis, and validated their involvement in IKK16/SGI1027-mediated paraptosis with a cellular functional assay. Furthermore, the proteomics data revealed a novel set of proteins previously unassociated with paraptosis. We have substantiated our proteomics findings through western blotting and immunocytochemistry in breast and colorectal cancer cell lines, demonstrating similar effects. Moreover, we have shown that combining paraptosis-inducing compounds with anti-cancer drugs can reduce the required overall dosage concentration while preserving therapeutic efficacy, potentially revolutionizing cancer treatment.