Design, synthesis and biological evaluation of novel peptides as potential agents with anti-tumor and multidrug resistance-reversing activities
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Tumor chemotherapy is an important mean in the clinical treatment of metastatic cancer,but low selectivity and drug resistance restrict its clinical application. BP100 is a multifunctional membrane-active peptide with high antimicrobial activity. We selected BP100 as a lead peptide, designed and synthesized a series of BP100 analogs through solid-phase synthesis. Amongst them, peptides with the Tyr10 residue substituted by leucine and histidine showed the highest anti-cancer activity. Further experiments revealed that BP100 and its analogs could disrupt the cell membrane and trigger the cytochrome C release into cytoplasm, which ultimately resulted in apoptosis. Meanwhile, BP100 and its analogs also exhibited effective anti-tumor activity against multidrug-resistant cells, showing multidrug resistance-reversing effects. In conclusion, these peptides might be promising candidates for cancer therapy.
KeywordsAnti-cancer Multidrug resistance-reversing effects Membrane-disruption Antimicrobial peptides
This study was supported by Grants from the National Natural Science Foundation of China (Grants 81673299 and 81273376).
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Conflict of interest
The authors have no conflicts of interest to declare.
- de Kroon AI, Dolis D, Mayer A, Lill R, de Kruijff B (1997) Phospholipid composition of highly purified mitochondrial outer membranes of rat liver and Neurospora crassa. Is cardiolipin present in the mitochondrial outer membrane? Biochim Biophys Acta (BBA) Biomembr 1325(1):108–116CrossRefGoogle Scholar
- Mai JC, Mi Z, Kim S-H, Ng B, Robbins PD (2001) A proapoptotic peptide for the treatment of solid tumors. Can Res 61(21):7709–7712Google Scholar
- Manzini MC, Perez KR, Riske KA, Bozelli JC, Santos TL, da Silva MA, Saraiva GK, Politi MJ, Valente AP, Almeida FC (2014) Peptide: lipid ratio and membrane surface charge determine the mechanism of action of the antimicrobial peptide BP100. Conformational and functional studies. Biochim Biophys Acta (BBA) Biomembr 1838(7):1985–1999CrossRefGoogle Scholar