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Bovine HDL and Dual Domain HDL-Mimetic Peptides Inhibit Tumor Development in Mice
Feng Su1, Anantharamaiah Gm2, Mayakonda N Palgunachari2
1Department of Obstetrics and Gynecology, David Geffen School of Medicine, the University of California at Los Angeles, Los Angeles, CA 90095, USA.
Journal of Cancer Research and Therapeutic Oncology
|May 29, 2020
Summary
Bovine HDL and dual-domain peptides show promise in treating ovarian and colon cancers. These compounds inhibit tumor growth and reduce pro-inflammatory lipids, suggesting novel therapeutic potential for epithelial adenocarcinomas.
Area of Science:
- Biochemistry
- Oncology
- Immunology
Background:
- High-density lipoprotein (HDL) apolipoproteins are implicated in managing inflammatory conditions, including cancer.
- Epithelial adenocarcinomas, such as ovarian and colon cancers, represent significant health challenges.
- Understanding novel therapeutic targets for these cancers is crucial.
Purpose of the Study:
- To investigate the anti-cancer effects of bovine HDL (bHDL) and specific dual-domain peptides (AEM-28, AEM-28-2, HM-10/10).
- To evaluate their impact on tumor growth and development in mouse models of ovarian and colon cancer.
- To explore potential mechanisms underlying their anti-tumor activity, focusing on lysophosphatidic acid (LPA) levels.
Main Methods:
- Utilized mouse models for ovarian (ID8) and colon (CT26) cancer.
- Administered bHDL and dual-domain peptides via subcutaneous injection or dietary incorporation.
- Assessed tumor burden, tumor growth, tumor dissemination, and plasma LPA levels.
- Evaluated peptide effects on cancer cell viability in vitro, including normal cell controls.
Main Results:
- bHDL inhibited lung tumor development in a colorectal cancer model and reduced tumor burden in an ovarian cancer model.
- Dual-domain peptides demonstrated varying degrees of inhibition on the viability of mouse and human ovarian and colon cancer cell lines, sparing normal cells.
- Subcutaneous or dietary administration of dual-domain peptides reduced tumor burden, growth, and dissemination in mice.
- Significant reductions in plasma lysophosphatidic acid (LPA) levels were observed in mice treated with bHDL and dual-domain peptides.
Conclusions:
- bHDL and dual-domain peptides exhibit significant anti-tumor activity against ovarian and colon cancer models.
- Reduced LPA levels suggest a potential mechanism involving the modulation of pro-inflammatory lipids.
- HDL-based therapeutics, particularly apolipoprotein-derived agents, represent promising novel treatments for epithelial adenocarcinomas.
