A Previously Unrecognized  Mechanism in Cancer-Specific Apoptosis

Sigma 1 Receptor Mediates IL-24 Induced Cancer

Apoptosis through Lipid Raft Formation: an in vitro and

in silico approach

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Interleukin-24 (IL-24) is an immunomodulatory cytokine

with tumor-suppressing activity. The objective was to identify

the molecular mechanisms underlying IL-24’s antitumor

activity with Sigma 1 receptor (Sig-1R) to induce cancer

apoptosis, a process that cancer cells typically override. MTT

assay and immunofluorescence procedures were performed

and it was found that IL-24 induces cancer apoptosis by

Sig-1R translocation to lipid rafts in the plasma membrane of

cancer cells, demonstrating a previously unrecognized role of IL-24 in lipid raft formation. The results of comparative in silico modeling showed that when wild IL-24 binds with Sig-1R, it is a higher energy and low cluster size interaction than when a targeted IL-24 peptide (IL-24P) binds with Sig-1R, which is significant as an IL-24 peptide would more easily access a cancer cell than a wild IL-24 would. The results presented in this research are significant towards creating personalized precision therapies and combined drug therapies to combat cancer, trumping typical cancer therapies by targeting multiple cell signaling pathways that allow for tumorigenic cell proliferation and by targeting the individual needs of each patient. It is cancer cell specific, so it wouldn't target healthy cells, which occurs in the typically used cancer therapies today, such as chemotherapy and tubulin targeting therapies. The unique methodology that was developed in this study can be slightly adapted for use with multiple other cellular diseases and IL-24:Sig-1R related diseases, including neurodegenerative, inflammatory, infectious, psychological, and retinal diseases.