Effect of dimerized melittin on gastric cancer cells and antibacterial activity
Melittin is the peptide toxin found in bee venom and is effective against cancer cells. To enhance its activity, a branched dimeric form of melittin was designed. The monomeric form of the peptide was more cytotoxic against gastric cancer cells at low concentrations (1–5 μM) than the dimer form, while the cytotoxic effect was comparable at higher concentrations (10 μM). Confocal microscopy showed that both the monomer and dimer forms of melittin with fluorescent label at the C terminus penetrated the cytoplasm and localized at the cell nucleus and disrupted the cell membrane. The results indicated that both peptides localized in the nucleus and no significant difference in penetration was observed between monomer and dimer of melittin. Although the C and N termini are important for melittin activity, using C terminus for dimerization of the peptide resulted in similar activity for the monomer and dimer against bacteria and gastric cancer cells.
KeywordsLytic peptide Cytotoxicity Confocal microscopy Cell membranes
FS acknowledges the Australian Research Council for award of grant DP140102127.
Compliance with ethical standards
Conflict of interest
The authors do not have potential conflicts of interest.
Research involving Human Participants and/or Animals
This research did not involve Human Participants and/or Animals and does not require Informed Consent.
Supplementary material 1 (WMV 17685 kb)
- Barrera G (2012) Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol 2012:21Google Scholar
- Jamasbi E, Ciccotosto GD, Tailhades J, Robins-Browne RM, Ugalde CL, Sharples RA, Patil N, Wade JD, Hossain MA, Separovic F (2015) Site of fluorescent label modifies interaction of melittin with live cells and model membranes. Biochimica et Biophysica Acta 1848(10 Pt A):2031–2039CrossRefPubMedGoogle Scholar
- Li W, O’Brien-Simpson NM, Tailhades J, Pantarat N, Dawson RM, Otvos L Jr, Reynolds EC, Separovic F, Hossain MA, Wade JD (2015) Multimerization of a proline-rich antimicrobial peptide, CHEX-Arg20, alters its mechanism of interaction with the Escherichia coli membrane. Chem Biol 22(9):1250–1258CrossRefPubMedGoogle Scholar
- Li W, O’Brien-Simpson NM, Yao S, Tailhades J, Reynolds EC, Dawson RM, Otvos L Jr, Hossain MA, Separovic F, Wade JD (2017) C-Terminal modification and multimerization increase the efficacy of a proline-rich antimicrobial peptide. Chemistry (Weinheim an der Bergstrasse, Germany) 23(2):390–396Google Scholar
- Riss TL, Moravec RL, Niles AL, Duellman S, Benink HA, Worzella TJ, Minor L (2013) Cell viability assays. In: Sittampalam GS, Coussens NP, Brimacombe K, et al (eds) Assay guidance manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2004. http://europepmc.org/books/NBK144065
- Wu D, Yotnda P (2011) Production and detection of reactive oxygen species (ROS) in cancers. J Vis Exp JoVE 57:3357Google Scholar