The antimicrobial peptide pardaxin exerts potent anti-tumor activity against canine perianal gland adenoma

Pan, Chieh-Yu; Lin, Chao‐Nan; Chiou, Ming‐Tang; Yu, Chao; Chen, Jyh-Yih; Chien, Chun-Hsien

doi:10.18632/oncotarget.2959

Cited by 26 publications

(15 citation statements)

References 40 publications

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“…As one type of potential cancer therapeutics, some CAPs have been reported to show selective cytotoxicity and antitumor capabilities against a variety of cancer cell types. Previous studies have provided the modes of action for these CAPs, which involve the disruption or poration of the plasma membranes and other intracellular events 11 , 23 – 26 . However, due to the complex bio-diversities of various cancer cells and the physicochemical properties of CAPs, the detailed cellular processes of these cancer-targeted CAPs, including the cancer cells surface binding and cellular uptaking, are still far from being clearly understood.…”

Section: Discussionmentioning

confidence: 99%

Cell surface binding, uptaking and anticancer activity of L-K6, a lysine/leucine-rich peptide, on human breast cancer MCF-7 cells

Che

Dong

Zhang

et al. 2017

Sci Rep

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Cell surface binding and internalization are critical for the specific targeting and biofunctions of some cationic antimicrobial peptides (CAPs) with anticancer activities. However, the detailed cellular process for CAPs interacting with cancer cells and the exact molecular basis for their anticancer effects are still far from being fully understood. In the present study, we examined the cell surface binding, uptaking and anti-cancer activity of L-K6, a lysine/leucine-rich CAP, in human MCF-7 breast cancer cells. We found that L-K6 preferentially interact with MCF-7 cells. This tumor-targeting property of L-K6 might be partially due to its interactions with the surface exposed and negatively charged phosphatidylserine. Subsequently, L-K6 could internalize into MCF-7 cells mainly through a clathrin-independent macropinocytosis, without significant cell surface disruption. Finally, the internalized L-K6 induced a dramatic nuclear damage and MCF-7 cell death, without significant cytoskeleton disruption and mitochondrial impairment. This cytotoxicity of L-K6 against MCF-7 cancer cells could be further confirmed by using a mouse xenograft model. In summary, all these findings outlined the cellular process and cytotoxicity of L-K6 in MCF-7 cancer cells, and might help understand the complicated interactions between CAPs and cancer cells.

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Section: Discussionmentioning

confidence: 99%

Cell surface binding, uptaking and anticancer activity of L-K6, a lysine/leucine-rich peptide, on human breast cancer MCF-7 cells

Che

Dong

Zhang

et al. 2017

Sci Rep

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“…Pardaxin with a lytic action has potent activity against canine perianal gland adenomas and thus has potential veterinary application [ 61 ]. Bullacta exarata peptides BEPT II and BEPT II-1 manifested potent apoptotic activity toward PC-3 cells [ 62 ].…”

Section: Marine Peptides With Different Bioactivitiesmentioning

confidence: 99%

Marine Peptides: Bioactivities and Applications

2015

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Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products.

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“…They demonstrate activities against diverse pathogens, including bacteria, viruses, fungi, mycoplasma, and parasites [ 2 , 3 ]. The positively-charged characteristics of AMPs allow them to penetrate and interact with anionic molecules on the surface of cancer cell membrane, such as phosphatidylserine and terminal sialic acids, including N-linked and O-linked glycans, thus causing cytotoxic membrane disruption to certain cancer types, but not to normal cells [ 4 , 5 ]. However, the fundamental mechanisms for AMP-mediated membrane collapse and tumor-specific cytotoxicity are poorly understood at present.…”

Section: Introductionmentioning

confidence: 99%

The Use of a Liposomal Formulation Incorporating an Antimicrobial Peptide from Tilapia as a New Adjuvant to Epirubicin in Human Squamous Cell Carcinoma and Pluripotent Testicular Embryonic Carcinoma Cells

Lo¹,

Lee

2015

IJMS

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This study aims to explore the effects and mechanisms of hepcidin, a potential antimicrobial peptide from Tilapia, and epirubicin (Epi), an antineoplastic agent, on the generation of reactive oxygen species (ROS) and link the ROS levels to the reversal mechanisms of multidrug resistance (MDR) by epirubicin and hepcidin in human squamous cell carcinoma SCC15 and human embryonal carcinoma NT2D1 cells. The cells, pretreated with hepcidin, epirubicin, or a combination of these compounds in PEGylated liposomes, were used to validate the molecular mechanisms involved in inhibiting efflux transporters and inducing apoptosis as evaluated by cytotoxicity, intracellular accumulation, mRNA levels, cell cycle distribution, and caspase activity of this combination. We found that hepcidin significantly enhanced the cytotoxicity of epirubicin in liposomes. The co-incubation of epirubicin with hepcidin in liposomes intensified the ROS production, including hydrogen peroxide and superoxide free radicals. Hepcidin significantly increased epirubicin intracellular uptake into NT2D1 and SCC15 cells, as supported by the diminished mRNA expressions of MDR1, MDR-associated protein (MRP) 1, and MRP2. Hepcidin and/or epirubicin in liposomes triggered apoptosis, as verified by the reduced mitochondrial membrane potential, increased sub-G1 phase of cell cycle, incremental populations of apoptosis using annexin V/PI assay, and chromatin condensation. As far as we know, this is the first example showing that PEGylated liposomal TH1-5 and epirubicin gives rise to cell death in human squamous carcinoma and testicular embryonic carcinoma cells through the reduced epirubicin efflux via ROS-mediated suppression of P-gp and MRPs and concomitant initiation of mitochondrial apoptosis pathway. Hence, hepcidin in PEGylated liposomes may function as an adjuvant to anticancer drugs, thus demonstrating a novel strategy for reversing MDR.

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The antimicrobial peptide pardaxin exerts potent anti-tumor activity against canine perianal gland adenoma

Cited by 26 publications

References 40 publications

Cell surface binding, uptaking and anticancer activity of L-K6, a lysine/leucine-rich peptide, on human breast cancer MCF-7 cells

Cell surface binding, uptaking and anticancer activity of L-K6, a lysine/leucine-rich peptide, on human breast cancer MCF-7 cells

Marine Peptides: Bioactivities and Applications

The Use of a Liposomal Formulation Incorporating an Antimicrobial Peptide from Tilapia as a New Adjuvant to Epirubicin in Human Squamous Cell Carcinoma and Pluripotent Testicular Embryonic Carcinoma Cells

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