Chemokine-derived oncolytic peptide induces immunogenic cancer cell death and significantly suppresses tumor growth

Natsuki Furukawa; Wendy Yang; Alex R Chao; Akash Patil; Adam C Mirando; Niranjan B Pandey; Aleksander S Popel

doi:10.1038/s41420-024-01932-5

Chemokine-derived oncolytic peptide induces immunogenic cancer cell death and significantly suppresses tumor growth

Cell Death Discov. 2024 Apr 2;10(1):161. doi: 10.1038/s41420-024-01932-5.

Authors

Natsuki Furukawa¹, Wendy Yang², Alex R Chao², Akash Patil², Adam C Mirando², Niranjan B Pandey², Aleksander S Popel^{2

3}

Affiliations

¹ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. nfurukawa@jhmi.edu.
² Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Chemokinostatin-1 (CKS1) is a 24-mer peptide originally discovered as an anti-angiogenic peptide derived from the CXCL1 chemokine. Here, we demonstrate that CKS1 acts not only as an anti-angiogenic peptide but also as an oncolytic peptide due to its structural and physical properties. CKS1 induced both necrotic and apoptotic cell death specifically in cancer cells while showing minimal toxicity in non-cancerous cells. Mechanistically, CKS1 disrupted the cell membrane of cancer cells quickly after treatment and activated the apoptotic pathway at later time points. Furthermore, immunogenic molecules were released from CKS1-treated cells, indicating that CKS1 induces immunogenic cell death. CKS1 effectively suppressed tumor growth in vivo. Collectively, these data demonstrate that CKS1 functions as an oncolytic peptide and has a therapeutic potential to treat cancer.

Abstract

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