SSTP1, a Host Defense Peptide, Exploits the Immunomodulatory IL6 Pathway to Induce Apoptosis in Cancer Cells

• DOI: 10.3389/fimmu.2021.740620
• Publication Date: 2021-11-19T04:42:23Z
• Authors: Shyla Gopalakrishnan; Soumya Krishnan Uma; Gayathri Mohan; Amrutha Mohan; Geetha Shanmugam; Vineeth T. V. Kumar; Sreekumar J; Sivakumar K. Chan...; Dileep Vasudevan; Sai Ravi Chandra ...; Shijulal Nelson S...; Sanil George; Tessy Thomas Mali...
• Keywords: 0301 basic medicine; host defense peptides; immunoregulation; Interleukin-6; Immunology; apoptosis; Apoptosis; temporins; RC581-607; Amphibian Proteins; 3. Good health; 03 medical and health sciences; Cell Line, Tumor; Neoplasms; cancer; Animals; Humans; Immunologic diseases. Allergy; Anura; JNK/AP1 pathway; Antimicrobial Cationic Peptides

While the immunomodulatory pathways initiated in immune cells contribute to therapeutic response, their activation cancer play a role progression. Also, many of aberrantly expressed immunomodulators on are considered as targets. Here, we introduce host defense peptide (HDP), known immuomodulator, agent target them. The cationic peptides (HDPs), an integral part innate system, possess membranolytic activity, which imparts antimicrobial and antitumor efficacy it. They act by activating cells. Though function has been recently reassigned immunoregulation, activity is still attributed its activity. This membrane pore formation ability, proportional concentration peptide, also leads side effects like hemolysis, limiting application. So, despite identification variety anticancer HDPs, clinical utility limited. HDPs shown exert through specific targets cells, unknown. We show that SSTP1, novel HDP identified shotgun cloning, binds active IL6/IL6Rα/gp130 complex rearranging site residues. In contrast IL6 blockers inhibiting JAK/STAT SSTP1 shifts proliferative IL6/JAK/STAT signaling apoptotic IL6/JNK/AP1 pathway. IL6Rα-overexpressing induces apoptosis at low JNK pathway, without causing significant disruption. highlight importance apoptosis, apart from established cell regulation proliferation. Our study suggests for promising might lead new drugs targeted therapy.