SHLP-6 (Small Humanin-Like Peptide 6) is a mitochondrial-derived peptide with unique dual nature—promoting apoptosis in cancer cells while protecting normal cells.
Unique Pro-Apoptotic Properties
Unlike cytoprotective SHLP-2 and SHLP-3, SHLP-6 increases apoptosis in:
- NIT-1 (murine pancreatic beta cells)
- 22Rv1 (human prostate cancer cells)
Molecular Interactions
Molecular docking studies reveal binding affinities:
Pro-Apoptotic
- Caspase 8: -77.6 kcal/mol
- Cytochrome C: -53.2 kcal/mol
- DRP1: -47.7 kcal/mol (promotes mitochondrial fission/apoptosis)
Regulatory
- SIRT1: -49.1 kcal/mol
- IGF-1: -58.7 kcal/mol
- Insulin receptor: -66.4 kcal/mol
Cancer Research Implications
SHLP-6 shows selective toxicity—apoptotic in cancer cells while protecting normal cells against mitochondria-mediated apoptosis.
Paradoxical Protective Effects
In zebrafish larvae exposed to oxidative stress:
- Reduced developmental toxicity
- Improved antioxidant enzyme levels (SOD, CAT)
- Improved acetylcholinesterase levels
Evolutionary Conservation
Strong sequence conservation across vertebrates suggests significant biological importance.