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Pardaxin induced apoptotic cell death in HT-1080 cells. HT1080 cells were treated with 15 μg/mL pardaxin. Pardaxin-treated and untreated cells were harvested after 3, 6, and 12 h for annexin V (AV)/propidium iodide (PI) staining, examined by flow cytometry, and analyzed by FlowJo using bi-exponential scaling. (A) The x-axis is the annexin V signal which represents the expression of phosphatidylserine on the membrane when cells undergo apoptosis. The y-axis is the PI signal which represents the loss of membrane integrity of cells undergoing necrosis. The lower left, upper left, lower right, and upper right portions respectively indicate viable, necrotic, apoptotic, and secondary necrotic cells. Cells treated with 15 μg/mL pardaxin for (B) 3, (C) 6, and (D) 12 h, were analyzed by flow cytometry in triplicate; (E) The sum of apoptotic and secondary necrotic cells was calculated and represents all apoptotic events.
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Pardaxin is an antimicrobial peptide (AMP) that was first isolated from secretions of the Red Sea Moses sole. The role of pardaxin in inducing apoptosis for preventing cancer has not yet been investigated. In the present study, we examined the antitumor activity of pardaxin against human fibrosarcoma HT-1080 cells; pardaxin inhibited cell prolifera...
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... annexin V/PI assay was performed to detect the type of cell death induced by pardaxin. With 15 μg/mL pardaxin treatment for 12 h, the cell population was distributed in the viable portion to the apoptotic and secondary necrotic portions, and post-apoptotic events ( Figure 2A). Apoptotic cells significantly increased from 6 h of treatment, and secondary necrotic cells were subsequently elevated at 12 h ( Figure 2B-D). ...
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... 15 μg/mL pardaxin treatment for 12 h, the cell population was distributed in the viable portion to the apoptotic and secondary necrotic portions, and post-apoptotic events ( Figure 2A). Apoptotic cells significantly increased from 6 h of treatment, and secondary necrotic cells were subsequently elevated at 12 h ( Figure 2B-D). Totals of apoptotic cells (apoptotic and secondary necrotic) significantly increased to 16.67% at 6 h and 39.40% at 12 h ( Figure 2E). ...
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... cells significantly increased from 6 h of treatment, and secondary necrotic cells were subsequently elevated at 12 h ( Figure 2B-D). Totals of apoptotic cells (apoptotic and secondary necrotic) significantly increased to 16.67% at 6 h and 39.40% at 12 h ( Figure 2E). ...
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... indicates that the MMP was diminished and Cyt c was released into the cytosol of HT-1080 cells after pardaxin treatment ( Figure 5), which might have been due to the pore-forming ability of intracellular pardaxin in mitochondrial membranes [33]. The release of Cyt c from mitochondria into the cytosol exhibited a signature of a mitochondrion-mediated apoptotic pathway which was observed in this study (Figures 2 and 3). Subsequently, it in turn triggered activation of caspases 3/7 (Figure 4). ...
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Temporin-1CEa is an antimicrobial peptide isolated from the skin secretions of the Chinese brown frog (Rana chensinensis). We have previously reported the rapid and broad-spectrum anticancer activity of temporin-1CEa in vitro. However, the detailed mechanisms for temporin-1CEa-induced cancer cell death are still weakly understood. In the present st...
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... The pardaxin is originally a secretion from Pardachirus marmoratus for defense purposes (Lazarovici 2002). The subsequent research revealed the antimicrobial effects of pardaxin (Oren and Shai 1996;Thennarasu and Nagaraj 1996;Lin et al. 2013) and more recent discoveries of the dual effects of this bioactive peptide gradually led to the discovery of its anticancer properties as well (Hsu et al. 2011;Huang et al. 2011;Wu et al. 2012;Han et al. 2015). However, as mentioned earlier, the toxic effects of pardaxin on sheep and human red blood cells were believed to restrain its eligibility as an alternative anticancer drug (Hsu et al. 2011;Lin et al. 2013). ...
... Furthermore, in murine fibrosarcoma cells, pardaxin demonstrated antitumor activity effectively when the concentration is greater than 13 μg/mL (4.7 μM), hence further supporting its potential as an anticancer agent (Wu et al. 2012). On the other hand, the treatment of pardaxin on human fibrosarcoma for 24 h demonstrated an IC 50 value of 14.52 ± 0.18 μg/mL (5.2 μM) (Huang et al. 2011). In contrast to this study, its mutant form, LL13 has exhibited a distinct characteristic, as evidenced by a higher IC 50 value recorded at 23.801 ± 4.303 μM in its interaction with HepG2 cells. ...
Liver cancer is a worldwide issue that also affects the Malaysian population. The occurrence is closely related to risk factors like chronic infections and environmental exposures. Due to the toxicity of conventional therapeutic drugs for liver cancer, bioactive peptides have emerged as a popular alternative anticancer agent. Although the full-length pardaxin from Pardachirus marmoratus was proven with anticancer effects, its concurrent haemolytic effects are yet to be resolved. Therefore, this study utilized in silico and in vitro analyses to assess cytotoxic effects induced by the shortened pardaxin derivatives. The in silico findings led to the discovery of a series of shortened pardaxin derivatives with 13 amino acids, where single residue replacement prediction by bioinformatics tools was done on the shortened sequences. Among the top five shortened derivatives, the derivative where amino acid threonine was replaced by proline, was identified as the most potential candidate, namely LL13. The LL13 peptide was predicted with improved anticancer effects, non-toxic, and alleviated haemolytic effects as compared to its parental peptide. The subsequent cytotoxicity testing further validated its selective toxicity against liver cancer cells, HepG2 cells, with relatively lower killing effects on the normal cells, Vero cells. These in vitro findings validated the in silico predictions and also indicated that this peptide has potential as an anticancer drug with selective targeting capabilities. In conclusion, this study has highlighted the potential of using a combination of in silico and in vitro approaches to discover potentially shortened peptides as a novel therapeutic option for liver cancer treatment.
... Furthermore, human fibrosarcoma cells, HT1080, were incubated with pardaxin only and the cancer cells started to undergo apoptosis through caspases-3/7 activation beginning at 6 h, and the apoptotic percentages of cells increased from 16.67 to 39.4% at 6 and 12 h, respectively. The same study also observed ROS overproduction and release of cytochrome C into the cytosol, indicating the activation of ROS-mediated mitochondrial pathway apoptosis in pardaxin-treated HT1080 (Huang et al. 2011). ...
The discovery of marine-derived compounds bloomed in recent years. Bioactive compounds can be extracted from marine creatures like seahorses, mollusks, aquatic plants, algae, or fishes. Numerous of these discovered compounds were proven with various therapeutic values, including antibacterial, antihypertensive, antioxidant, and anticancer properties. Pardaxin is one of the recently discovered bioactive peptides with dual antibacterial and anticancer effects. Pardaxin is a 33-amino acid peptide that is secreted by the Red Sea Moses, Pardachirus marmoratus, solely for defensive purposes. This peptide was determined as a cationic peptide that held an alpha-helical structure, and it is believed that these two characteristics contributed to the anticancer potential of pardaxin. Therefore, this article reviews the anticancer properties of pardaxin in terms of its cancer-killing mechanisms such as apoptosis, cell cycle arrest, and cell lysis. Besides, we also reviewed other potent therapeutic applications of pardaxin, including the use of pardaxin as an immunotherapy agent, drug carrier, and in cancer vaccines. This review aims to encourage the use of pardaxin as an anticancer agent in the medicinal field.
... Consistently, Smp43 upregulates apoptosis in A549 cells via regulating the mitochondrial apoptotic pathway ( Figure 5). This effect is similar to that of the antitumor capability of Pardaxin, an AMP isolated from secretions of the Red Sea Moses sole, which targets mitochondria and induces apoptosis by activating caspase-3/7 [33]. It is well-known that the kinase activity of CDK2/cyclin E is required for gene transcription and progression into and through the S phase, while CDK2/cyclin A and CDK1/cyclin A are necessary for progression through the S phase and into the G2 phase, respectively [34]. ...
Research has been conducted to investigate the potential application of scorpion venom-derived peptides in cancer therapy. Smp43, a cationic antimicrobial peptide from Scorpio maurus palmatus venom, has been found to exhibit suppressive activity against the proliferation of multiple cancer cell lines. However, its impact on non-small-cell lung cancer (NSCLC) cell lines has not been previously investigated. This study aimed to determine the cytotoxicity of Smp43 towards various NSCLC cell lines, particularly A549 cells with an IC50 value of 2.58 μM. The results indicated that Smp43 was internalized into A549 cells through membranolysis and endocytosis, which caused cytoskeleton disorganization, a loss of mitochondrial membrane potential, an accumulation of reactive oxygen species (ROS), and abnormal apoptosis, cell cycle distribution, and autophagy due to mitochondrial dysfunction. Additionally, the study explored the in vivo protective effect of Smp43 in xenograft mice. The findings suggest that Smp43 has potential anticarcinoma properties exerted via the inducement of cellular processes related to cell membrane disruption and mitochondrial dysfunction.
... Studies using AMPs to induce apoptosis in different cancer cells have consistently demonstrated this typical biological feature, as seen in BB/BC inducing apoptosis and causing an increase in ROS levels in epidermal carcinoma cells A431 [14,15]. Similarly, AMP such as Bogorol B-JX from Br. Laterosporus can cause ROS accumulation in U-937 cells [11], another pentapeptide can induce apoptosis in HL-60 cells and increase their intracellular ROS levels [29], and the AMP CM4 has the same effect on breast cancer cells MX-1, MCF-7, and MDA-MB-231 [30,31]. A fluorescent probe DCFH-DA was utilized to quantify the levels of ROS, and the outcomes were presented in Figure 7. ...
... causing an increase in ROS levels in epidermal carcinoma cells A431 [14,15]. Similarly, AMP such as Bogorol B-JX from Br. Laterosporus can cause ROS accumulation in U-937 cells [11], another pentapeptide can induce apoptosis in HL-60 cells and increase their intracellular ROS levels [29], and the AMP CM4 has the same effect on breast cancer cells MX-1, MCF-7, and MDA-MB-231 [30,31]. To evaluate the mitochondrial membrane potential of BGC-823 cells, fluorescence probe JC-1, which exists in monomeric and aggregated forms, was used ( Figure 8). ...
... The addition of BB/BC has been shown to effectively decrease the mitochondrial membrane potential in BGC-823 cells, indicating their ability to induce early apoptosis in these cancer cells. These findings are consistent with those observed in epidermal carcinoma cells A431 [14,15] and other AMPs such as Pardaxin and AMP B11, which have been shown to induce early apoptosis in cancer cells HT-1080 and Hela, respectively [31,32]. With increasing concentrations and duration of BB/BC treatment, an upward trend in mitochondrial membrane potential was observed in BGC-823 cells, which may be attributed to the fact that BB/BC triggers apoptosis in these cells from early to late stages at increasing concentrations [11]. ...
Brevilaterins, antimicrobial peptides produced by Brevibacillus laterosporus, are regarded as excellent food preservatives and are popular as antimicrobial applications. Recent research has uncovered their potent cytotoxic effects against diverse cancer cells, thereby underscoring the pressing need for more extensive and intensive investigations into this use. In this study, we explored their novel function in inducing cytotoxicity to cancer cells and systematically investigated the mechanism of action of Brevilaterin B/C (BB/BC) in vivo. Proliferation, membrane permeability, and apoptotic rate were evaluated using CCK-8 assay, LDH assay, and Annexin V-FITC/PI kits. ROS levels and mitochondrial membrane potential were detected using the fluorescent probe DCFH-DA and JC-1. Our results demonstrated that both BB and BC at concentrations of 4–6 µg/mL significantly inhibited the proliferation and migration of gastric cancer cells BGC-823. Treatment with 4 µg/mL of BB/BC rapidly increased LDH levels in the supernatant of BGC-823 cells, leading to further investigation of the mechanism of apoptosis. We found that the apoptotic rate of BGC-823 cells significantly increased upon treatment with BB/BC, demonstrating their potent induction of apoptosis. BB/BC-induced ROS production in BGC-823 cells impaired their growth and induced apoptosis, indicating a close association between apoptosis and ROS elevation. Additionally, JC-1 aggregates rapidly accumulated after treatment with 4 µg/mL of BB/BC, suggesting changes in mitochondrial membrane potential and early apoptosis. Taken together, our findings revealed that BB and BC exhibit significant anticancer effects against gastric cancer cells, highlighting the promising potential of Brevilaterins as anticancer agents.
... For example, PNW [15], Polybia-MP1 [16], and Pardaxin [17] kill cancer cells by disrupting the cell membrane. Non-membranolytic mechanisms are mainly involved in ROS accumulation, DNA damage, mitochondrial membrane potential depolarization, autophagy, and apoptosis [18,19]. Pardaxin, an antimicrobial peptide isolated from secretions of the fish, the Red Sea Moses sole, triggered caspase-dependent, and ROS-mediated apoptosis in HT-1080 cells [18]. ...
... Non-membranolytic mechanisms are mainly involved in ROS accumulation, DNA damage, mitochondrial membrane potential depolarization, autophagy, and apoptosis [18,19]. Pardaxin, an antimicrobial peptide isolated from secretions of the fish, the Red Sea Moses sole, triggered caspase-dependent, and ROS-mediated apoptosis in HT-1080 cells [18]. In addition, FK-16 derived from LL-37 induced caspase-independent apoptosis and autophagy through the p53-Bcl-2/Bax cascade reaction common in colon cancer cells [20]. ...
... The anticancer effects of AMPs can follow different pathways, including ROS accumulation, mitochondrial membrane potential depolarization, induction of apoptosis, etc. [18,19]. It has been shown that an increase in cytoplasmic Ca 2+ can act as an apoptotic signal to initiate apoptosis [37]. ...
Cancer is one of the most common malignant diseases in the world. Hence, there is an urgent need to search for novel drugs with antitumor activity against cancer cells. AMP-17, a natural antimicrobial peptide derived from Musca domestica, has antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and fungi. However, its antitumor activity and potential mechanism of action in cancer cells remain unclear. In this study, we focused on evaluating the in vitro antitumor activity and mechanism of AMP-17 on leukemic K562 cells. The results showed that AMP-17 exhibited anti-proliferative activity on K562 cells with an IC50 value of 58.91 ± 3.57 μg/mL. The membrane integrity of K562 was disrupted and membrane permeability was increased after AMP-17 action. Further observation using SEM and TEM images showed that the cell structure of AMP-17-treated cells was disrupted, with depressions and pore-like breaks on the cell surface, and vacuolated vesicles in the cytoplasm. Furthermore, further mechanistic studies indicated that AMP-17 induced excessive production of reactive oxygen species and calcium ions release in K562 cells, which led to disturbance of mitochondrial membrane potential and blocked ATP synthesis, followed by activation of Caspase-3 to induce apoptosis. In conclusion, these results suggest that the antitumor activity of AMP-17 may be achieved by disrupting cell structure and inducing apoptosis. Therefore, AMP-17 is expected to be a novel potential agent candidate for leukemia treatment.
... Antimicrobial peptides for example alamethicin show barrel stave channeling. Huang et al., (2011) reported another pardaxin as another example as are protegrins (Brogden, 2005). ...
A biofilm results when various microorganisms form a microbial community. Most biofilms are complex in structure and can be diverse in species. The microbes communicate via cell signaling molecules (quorum sensing (QS)) mechanisms. Biofilms can be harmful, particularly in biological systems, as they are hard to eradicate and are resistant to anti-microbial compounds. Therefore, biofilms are a significant health-related threat across the world. Conventional methods used to combat biofilms, such as physical, chemical, antibiotics, antiseptics, etc. are often not effective and can cause environmental problems. So, various novel approaches are being proposed and adopted by the scientific community. Among these approaches, the use of nanoparticles (NPs) is a promising emerging system as even tough and complex biofilms can be eradicated because of their strong anti-microbial properties and mode of action. Bioactive compounds from natural sources, mostly plants, are already being used as anti-biofilm agents. Many compounds like halogenated furanones, 2-amminoimidazole alkaloids, and flavonoids have been isolated from plants and marine organisms that have high anti-biofilm properties. Because of their broad-spectrum activities and non-specific mechanism of action, anti-microbial peptides (AMPs) are also potential candidates. AMP-based anti-biofilm strategies like prophylactic and therapeutic strategies are proving helpful. The combination of NPs with these natural products is proving helpful in fighting biofilm-based infections. Similarly, the use of combinations of antimicrobial/antibiofilm agents in suitable proportions can help to eradicate the biofilms and cure the disorders caused by biofilms. This review provides information on the emerging trends and approaches for the eradication of biofilms and the treatment of medical disorders caused by biofilms.
... Similarly, C-phycocyanin from Spirulina platensis has been shown to trigger cyt c release and increase the activities of casps-2, -3, -4, -6, -8, -9, and -10 in HeLa cells with IC 50 of 80 μg mL −1 [65]. Pardaxin and FW523-3 have shown analogous effects with IC 50s of 15 and 0.45 μg mL −1 [66][67][68]. ...
... Aplidine from Aplidium albicans inhibited cell migration and invasiveness of ovarian 1A9 cells by inhibiting vascular endothelial growth factor-mediated (VEGF) and blocked the production of matrix metalloproteinases (MMP2 and MMP9) [113]. Pardaxin from fish showed a similar effect in HeLa cell lines [66,67]. ...
... Cryptophycins 1 in SKOV3 was found to induce DNA fragmentation [63]. Pardaxin induced DNA fragmentation in HeLa and HT-1080 cell lines [66,67]. C-phycocyanin from Spirulina platensis has been also shown to scavenge ROS, specifically peroxyl and hydroxyl radicals [119]. ...
Cervical and ovarian cancers contribute significantly to female morbidity and mortality worldwide. The current standard of treatment, including surgical removal, radiation therapy, and chemotherapy, offers poor outcomes. There are many side effects to traditional chemotherapeutic agents and treatment-resistant types, and often the immune response is depressed. As a result, traditional approaches have evolved to include new alternative remedies, such as natural compounds. Aquatic species provide a rich supply of possible drugs. The potential anti-cancer peptides are less toxic to normal cells and can attenuate multiple drug resistance by providing an efficacious treatment approach. The physiological effects of marine peptides are described in this review focusing on various pathways, such as apoptosis, microtubule balance disturbances, suppression of angiogenesis, cell migration/invasion, and cell viability. The review also highlights the potential role of marine peptides as safe and efficacious therapeutic agent for the treatment of cervical and ovarian cancers.
... The underlying mode of action may include Ca 2+ -stimulated nitric oxide production, Ca 2+ -stimulated increase in metabolic rate, Ca 2+ -induced cytochrome C (Cyt C) dissociation, Ca 2+ -induced opening of the permeability transition pore with the subsequent release of Cyt C, Ca 2+ -induced cardiolipin peroxidation, and Ca 2+ /calmodulin dependent protein kinase activation. Several marine peptides can change the Bcl-2/Bax ratio, activate caspases, and release Cyt C to induce cell apoptosis by stimulating Ca 2+ overload and ROS production in tumor cells [40]. In this study, we found that P6 suppressed CRC cell proliferation ( Figure 3) and induced cell apoptosis (Figure 4) by producing a concentration-dependent increase in intracellular Ca 2+ concentration ( Figure 5D,E). ...
... Pardaxin, a peptide consisting of 33 amino acid residues, is isolated from the secretions of a fish (Pardachirus marmoratus) found at the bottom of the Red Sea. Studies have shown that pardaxin can induce apoptosis in human fibrosarcoma HT-1080 cells, which is manifested by the increased activity of caspase-3, mitochondrial membrane potential changes, and the accumulation of reactive oxygen species (ROS) products [40]. P6 showed a similar effect, producing an increased activity of caspase-3 and mitochondrial membrane potential changes in CRC cells ( Figure 5B,C). ...
Colorectal carcinoma (CRC) is one of the major causes of cancer-related incidence and deaths. Here, we identified a novel antitumor peptide, P6, with a molecular weight of 2794.8 Da from a marine Chinese medicine, Arca inflata Reeve. The full amino acid sequence and secondary structure of P6 were determined by tandem mass de novo sequencing and circular dichroism spectroscopy, respectively. P6 markedly inhibited cell proliferation and colony formation, and induced apoptosis in CRC cells. Mechanistically, transcriptomics analysis and a serial functional evaluation showed that P6 induced colon cancer cell apoptosis through the activation of the p38-MAPK signaling pathway. Moreover, it was demonstrated that P6 exhibited antitumor effects in a tumor xenograft model, and induced cell cycle arrest in CRC cells in a concentration-dependent mode. These findings provide the first line of indication that P6 could be a potential therapeutic agent for CRC treatment.
... This resulting cytochrome c leakage into the cytosol of HT-1080 cells after pardaxin treatment has been related to the pore-forming ability in mitochondrial membranes [178]. Likewise, the release of cytochrome c from the mitochondria into the cytosol results in the mitochondrion-mediated apoptotic pathway [179] and the activation of caspases 3/7 [180]. ...
Nowadays, cancer has become the second highest leading cause of death, and it is expected to continue to affect the population in forthcoming years. Additionally, treatment options will become less accessible to the public as cases continue to grow and disease mechanisms expand. Hence, specific candidates with confirmed anticancer effects are required to develop new drugs. Among the novel therapeutic options, proteins are considered a relevant source, given that they have bioactive peptides encrypted within their sequences. These bioactive peptides, which are molecules consisting of 2–50 amino acids, have specific activities when administered, producing anticancer effects. Current databases report the effects of peptides. However, uncertainty is found when their molecular mechanisms are investigated. Furthermore, analyses addressing their interaction networks or their directly implicated mechanisms are needed to elucidate their effects on cancer cells entirely. Therefore, relevant peptides considered as candidates for cancer therapeutics with specific sequences and known anticancer mechanisms were accurately reviewed. Likewise, those features which turn certain peptides into candidates and the mechanisms by which peptides mediate tumor cell death were highlighted. This information will make robust the knowledge of these candidate peptides with recognized mechanisms and enhance their non-toxic capacity in relation to healthy cells and further avoid cell resistance.
... In general, AMPs (also called 'Host Defense Peptides' in higher eukaryotes), are a class of small biomolecules comprising low molecular weight (≤ 10,000 Daltons) oligopeptides, which are endowed with multi-functional roles, such as: direct and broad-spectrum antimicrobial activity; essential component of the innate immune system of higher eukaryotes as the first line of defense against microbial and parasitic invasions and immune-modulation such as modulation of leukocyte differentiation, chemo-attractant, insulinotropic, wound healing processes etc. [17,[21][22][23][24][25][26][27]. Besides these functions, AMPs attracted a lot of attention from researchers worldwide in investigating their potential as anticancer agents against different cancer models over the last two decades [28][29][30][31][32][33][34][35][36][37]. However, AMPs as colon cancer therapeutics have not been well reviewed and documented in scientific literature. ...
Despite recent advances in the treatment of colorectal cancer (CRC), low patient survival rate due to emergence of drug resistant cancer cells, metastasis and multiple deleterious side effects of chemotherapy, is a cause of public concern globally. To negate these clinical conundrums, search for effective and harmless novel molecular entities for the treatment of CRC is an urgent necessity. Since antimicrobial peptides (AMPs) are part of innate immunity of living beings, it is quite imperative to look for essential attributes of these peptides which may contribute to their effectiveness against carcinogenesis. Once identified, those characteristics can be suitably modified using several synthetic and computational techniques to further enhance their selectivity and pharmacokinetic profiles. Hence, this review analyses scientific reports describing the antiproliferative action of AMPs derived from several sources, particularly focusing on various colon cancer in vitro/in vivo investigations. On perusal of the literature, it appears that AMPs based therapeutics would definitely find special place in CRC therapy in future either alone or as an adjunct to chemotherapy provided some necessary alterations are made in their natural structures to make them more compatible with modern clinical practice. In this context, further in-depth research is warranted in adequate in vivo models.
