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PreprintCited by 10Cell death mechanisms and regulationAntimicrobial Peptides and ActivitiesChemical Synthesis and Analysis

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

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Furukawa, Natsuki, Yang, Wendy, Chao, Alex, Patil, Akash, Mirando, Adam, Pandey, Niranjan, Popel, Aleksander·2023·Cell Death Discovery
DOI 10.21203/rs.3.rs-3335225/v1PMC PMC10987543

Preprint — published as 10.1038/s41420-024-01932-5 · Paper page

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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 is a unique peptide that functions both as an anti-angiogenic peptide and as an oncolytic peptide and has a therapeutic potential to treat cancer.

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Metadata

Authors
Furukawa, N., Yang, W., Chao, A., Patil, A., Mirando, A., Pandey, N., & Popel, A.
Affiliations
Johns Hopkins University (US)
Corresponding author
Furukawa, Natsuki
ORCID
Venue
Cell Death Discovery
Publisher
Springer Science and Business Media LLC
Published
2023-10-03
Volume
10
Issue
1
Pages
161-161
ISSN
2058-7716 (ISSN-L)
DOI
10.21203/rs.3.rs-3335225/v1
PMC
PMC10987543
OpenAlex
W4393396983
Cited by
10
References
1
Citations by year
2026: 4 · 2025: 4 · 2024: 2
FWCI
1.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death Discovery (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Health and Human Services (P30CA006973, R01 CA138264, S10OD016374)
  • Johns Hopkins University (P30CA006973)
  • National Institutes of Health (1s10od016374-01, CA006973)
  • National Cancer Institute (R01CA138264, P30CA006973)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
Keywords
oncolytic peptide, immunogenic cell death, anti-angiogenic peptides, apoptosis, necrosis, cell membrane damage, tumor growth inhibition, cancer therapy

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