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Antitumor activity of HPA3P through RIPK3-dependent regulated necrotic cell death in colon cancer

Eugene Cho1, Jong-Kook Lee1, Eunji Park1

  • 1Department of Biomedical Science, Chosun University, Gwangju, Korea.

Oncotarget
|March 1, 2018
PubMed

Insights

The antimicrobial peptide HPA3P shows anticancer potential in colon cancer by inducing necrosis, a programmed cell death. This peptide enhances chemotherapy and may treat other cancers.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • The antimicrobial peptide HPA3 demonstrates anticancer effects in gastric cancer and leukemia.
  • Mechanisms of HPA3's anticancer activity and its efficacy in other cancer types are largely unknown.

Purpose of the Study:

  • To investigate the anticancer activity of HPA3 and its analogues in colon cancer.
  • To elucidate the molecular mechanisms underlying HPA3's anticancer effects in colon cancer.

Main Methods:

  • Assessing cell viability reduction in colon cancer cells treated with HPA3 and analogues.
  • Investigating cell death through necrosis markers (e.g., cellular content release, PI staining, HMGB1 release).
  • Evaluating the role of key necroptosis proteins (RIPK3, MLKL) using inhibition and knockdown approaches.

Main Results:

  • HPA3P significantly decreased colon cancer cell viability, unlike HPA3 and HPA3P2.
  • The reduction in cell viability was mediated by necrosis, evidenced by cellular content and HMGB1 release.
  • Inhibition or knockdown of RIPK3 and MLKL attenuated HPA3P-induced cell death.
  • HPA3P enhanced the efficacy of chemotherapeutic agents and showed activity in other cancer cell types.

Conclusions:

  • HPA3P induces colon cancer cell death via necrosis, involving RIPK3 and MLKL.
  • HPA3P exhibits potential as a novel anticancer agent for colon cancer treatment.
  • HPA3P may serve as a valuable adjunct to chemotherapy and has broader applicability in cancer therapy.
Keywords:
HPA3PRIPK3antitumor activitynecroptosispeptide

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