Piscidin-1, an Antimicrobial Peptide from Fish (Hybrid Striped Bass<i>Morone saxatilis</i>x<i>M. chrysops</i>), Induces Apoptotic and Necrotic Activity in HT1080 Cells

Lin, Heng Ju; Huang, Tsui-Chin; Muthusamy, Sasikala; Lee, Jheng Fong; Duann, Yeh Fang; Lin, Cheng Hui

doi:10.2108/zsj.29.327

Cited by 55 publications

(59 citation statements)

References 18 publications

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“…Previously it has been reported that piscidin-1, a cationic peptide isolated from the mast cells of hybrid striped bass (23), also causes apoptosis and necrosis at a low concentration and necrotic effect at a high concentration for a short period in HT1080 cells (24). Piscidin-1 has a net charge of +3 and HaA4 has a net charge of +2 at pH 7.0, which might function in the anticancer activity.…”

Section: Haa4 Induces Apoptosis and Necrosis In Leukemia Cellsmentioning

confidence: 99%

Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis

Kim

Lee

Kwon

et al. 2013

International Journal of Oncology

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Abstract.Harmoniasin is a defensin-like antimicrobial peptide identified from the ladybug Harmonia axyridis. Among the synthetic homodimer peptide analogues derived from harmoniasin, HaA4 has been found to have antibacterial activity without hemolytic activity. In this study, we investigated whether HaA4 has anticancer activity against human leukemia cell lines such as U937 and Jurkat cells. HaA4 manifested cytotoxicity and decreased the cell viability of U937 and Jurkat cells in MTS assay and LDH release assay. We found that HaA4 induced apoptotic and necrotic cell death of the leukemia cells using flow cytometric analysis, acridine orange/ethidium bromide staining and nucleosomal fragmentation of genomic DNA. Activation of caspase-7 and -9 and fragmentation of poly (ADP-ribose) polymerase was detected in the HaA4-treated leukemia cells, suggesting induction of a caspase-dependent apoptosis pathway by HaA4. Caspase-dependent apoptosis was further confirmed by reversal of the HaA4-induced viability reduction by treatment of Z-VAD-FMK, a pan-caspase inhibitor. In conclusion, HaA4 caused necrosis and caspase-dependent apoptosis in both U937 and Jurkat leukemia cells, which suggests potential utility of HaA4 as a cancer therapeutic agent.

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Section: Haa4 Induces Apoptosis and Necrosis In Leukemia Cellsmentioning

confidence: 99%

Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis

Kim

Lee

Kwon

et al. 2013

International Journal of Oncology

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“…The peptide exhibits antimicrobial activity against methicillin-resistant Staphylococcus aureus (24), viruses such as HIV-1 (25), fungi (26), and cancer cells (27). Like other AMPs, piscidin induces dye leakage in model membranes and membrane disruption is proposed to be its primary mechanism of action against bacteria (28,29).…”

Section: Introductionmentioning

confidence: 99%

“…The surfacebound structures of p1 were determined independently by ssNMR and all-atom molecular dynamics (MD) in two different bacterial cell mimics (30). Both methods yielded highly helical structures parallel to the membrane surface, and a [20][21][22][23][24][25][26][27][28][29][30] kink about the helical axis. Subsequent MD simulations demonstrated membrane thinning and induction of positive spontaneous curvature by p1 in 3:1 POPC/POPG bilayers (31).…”

Section: Introductionmentioning

confidence: 99%

Simulations of Membrane-Disrupting Peptides II: AMP Piscidin 1 Favors Surface Defects over Pores

Perrin

Cotten

et al. 2016

Biophysical Journal

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Antimicrobial peptides (AMPs) that disrupt bacterial membranes are promising therapeutics against the growing number of antibiotic-resistant bacteria. The mechanism of membrane disruption by the AMP piscidin 1 was examined with multimicrosecond all-atom molecular dynamics simulations and solid-state NMR spectroscopy. The primary simulation was initialized with 20 peptides in four barrel-stave pores in a fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol bilayer. The four pores relaxed to toroidal by 200 ns, only one porelike structure containing two transmembrane helices remained at 26 ms, and none of the 18 peptides released to the surface reinserted to form pores. The simulation was repeated at 413 K with an applied electric field and all peptides were surface-bound by 200 ns. Trajectories of surface-bound piscidin with and without applied fields at 313 and 413 K and totaling 6 ms show transient distortions of the bilayer/water interface (consistent with 31 P NMR), but no insertion to transmembrane or pore states.15 N chemical shifts confirm a fully surface-bound conformation. Taken together, the simulation and experimental results imply that transient defects rather than stable pores are responsible for membrane disruption by piscidin 1, and likely other AMPs.

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“…Piscidin-1 shows significant activity against bacteria, fungi, parasites, and cancer cells (1)(2)(3)(4)(5)(6)(7). It can also neutralize lipopolysaccharide (LPS)-induced proinflammatory responses in macrophage cells (5).…”

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confidence: 99%

Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity

Kumar

Tripathi

Kathuria

et al. 2016

Antimicrob Agents Chemother

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dPiscidin-1 possesses significant antimicrobial and cytotoxic activities. To recognize the primary amino acid sequence(s) in piscidin-1 that could be important for its biological activity, a long heptad repeat sequence located in the region from amino acids 2 to 19 was identified. To comprehend the possible role of this motif, six analogs of piscidin-1 were designed by selectively replacing a single isoleucine residue at a d (5th) position or at an a (9th or 16th) position with either an alanine or a valine residue. Two more analogs, namely, I5F,F6A-piscidin-1 and V12I-piscidin-1, were designed for investigating the effect of interchanging an alanine residue at a d position with an adjacent phenylalanine residue and replacing a valine residue with an isoleucine residue at another d position of the heptad repeat of piscidin-1, respectively. Single alanine-substituted analogs exhibited significantly reduced cytotoxicity against mammalian cells compared with that of piscidin-1 but appreciably retained the antibacterial and antiendotoxin activities of piscidin-1. All the single valine-substituted piscidin-1 analogs and I5F,F6A-piscidin-1 showed cytotoxicity greater than that of the corresponding alanine-substituted analogs, antibacterial activity marginally greater than or similar to that of the corresponding alanine-substituted analogs, and also antiendotoxin activity superior to that of the corresponding alanine-substituted analogs. Interestingly, among these peptides, V12I-piscidin-1 showed the highest cytotoxicity and antibacterial and antiendotoxin activities. Lipopolysaccharide (12 mg/kg of body weight)-treated mice, further treated with I16A-piscidin-1, the piscidin-1 analog with the highest therapeutic index, at a single dose of 1 or 2 mg/kg of body weight, showed 80 and 100% survival, respectively. Structural and functional characterization of these peptides revealed the basis of their biological activity and demonstrated that nontoxic piscidin-1 analogs with significant antimicrobial and antiendotoxin activities can be designed by incorporating single alanine substitutions in the piscidin-1 heptad repeat. Fish antimicrobial peptide (AMP) piscidin-1, which was discovered in 2001, possesses versatile biological activities. Piscidin-1 shows significant activity against bacteria, fungi, parasites, and cancer cells (1-7). It can also neutralize lipopolysaccharide (LPS)-induced proinflammatory responses in macrophage cells (5). Along with these desired biological activities, piscidin-1 also exhibits very significant lytic activity against normal mammalian cells, which is an obstacle for employing it as a lead molecule for the development of a new antimicrobial agent. Therefore, deciphering of the basis of cytotoxicity in piscidin-1 and the design of nontoxic analogs of piscidin-1 with desired biological activity were the objectives of the present investigation. Toward this end, we intended to identify the important primary sequence in piscidin-1 that could have a strong impact on its structural, functional, and ...

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Piscidin-1, an Antimicrobial Peptide from Fish (Hybrid Striped BassMorone saxatilisxM. chrysops), Induces Apoptotic and Necrotic Activity in HT1080 Cells

Cited by 55 publications

References 18 publications

Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis

Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis

Simulations of Membrane-Disrupting Peptides II: AMP Piscidin 1 Favors Surface Defects over Pores

Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity

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