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Phycocyanin, derived from marine algae, is known to have noteworthy antineoplastic properties. However, the underlying mechanism involved in phycocyanin-mediated anti-growth function on non-small cell lung cancer (NSCLC) cells is still ambiguous. Here, we investigated the mechanism of action of phycocyanin on H1299, A549, and LTEP-a2 cells. According to the results obtained, insulin receptor substrate 1 (IRS-1) expression was reduced by phycocyanin. Cell phenotype tests showed that siRNA knockdown of IRS-1 expression significantly inhibited the growth, migration, colony formation, but promoted the apoptosis of NSCLC cells. Meanwhile, phycocyanin and IRS-1 siRNA treatment both reduced the PI3K-AKT activities in NSCLC cells. Moreover, overexpression of IRS-1 accelerated the proliferation, colony formation, and migration rate of H1299, A549, and LTEP-a2 cells, which was contradicting to the knockdown results. Overall, this study uncovered a regulatory mechanism by which phycocyanin inhibited the growth of NSCLC cells via IRS-1/AKT pathway, laying the foundation for the potential target treatment of NSCLC.

Phycocyanin, derived from Spirulina platensis, is a type of natural antineoplastic marine protein. It is known that phycocyanin exerts anticancer effects on non-small-cell lung cancer (NSCLC) cells, but its underlying mechanism has not been elucidated. Herein, the antitumor function and regulatory mechanism of phycocyanin were investigated in three NSCLC cell lines for the first time: H358, H1650, and LTEP-a2. Cell phenotype experiments suggested that phycocyanin could suppress the survival rate, proliferation, colony formation, and migration abilities, as well as induce apoptosis of NSCLC cells. Subsequently, transcriptome analysis revealed that receptor-interacting serine/threonine-protein kinase 1 (RIPK1) was significantly down-regulated by phycocyanin in the LTEP-a2 cell, which was further validated by qRT-PCR and Western blot analysis in two other cell lines. Interestingly, similar to phycocyanin-treated assays, siRNA knockdown of RIPK1 expression also resulted in growth and migration inhibition of NSCLC cells. Moreover, the activity of NF-κB signaling was also suppressed after silencing RIPK1 expression, indicating that phycocyanin exerted anti-proliferative and anti-migratory function through down-regulating RIPK1/NF-κB activity in NSCLC cells. This study proposes a mechanism of action for phycocyanin involving both NSCLC apoptosis and down regulation of NSCLC genes.

Phycocyanin is a type of marine functional food additive, exerting a health care efficacy with no side effects. It has been shown that phycocyanin possesses anticancer function in non-small cell lung cancer (NSCLC) cells, but the underlying regulatory mechanism still remains unclear. Further investigation on the antineoplastic mechanism of phycocyanin would provide useful information on NSCLC treatment. In this study, we explored the in vitro function and mechanism of phycocyanin in three typical NSCLC cell lines, H1975, H1650, and LTEP-a2, for the first time. Phenotypic experiments showed that phycocyanin significantly induced the apoptosis as well as suppressed the growth of NSCLC cells. Transcriptome analysis suggested that toll/interleukin 1 receptor domain-containing adaptor protein (TIRAP) was significantly down-regulated by phycocyanin. Strikingly, similar to phycocyanin-treated assays, siRNA knockdown of TIRAP expression also resulted in the anti-proliferative phenomenon in NSCLC cells. In addition, the activity of NF-κB signaling was also suppressed after silencing TIRAP expression, revealing that phycocyanin exerted anti-proliferative function through down-regulating TIRAP/NF-κB activity in NSCLC cells. Collectively, this study has laid a theoretical basis on the treatment of NSCLC and the potential utilization of marine functional products.

Phycocyanin (PC), derived from cyanobacteria and Spirulina cells, is a type of natural antineoplastic marine protein. It has been reported that phycocyanin exerts an antitumor function in non-small cell lung cancer (NSCLC) cells, but the underlying mechanism has not been elucidated. In this research, a transcriptome study was performed to investigate the regulatory mechanisms of phycocyanin on human NSCLC A549 cells. The survival rate and proliferation ability of A549 cells were markedly reduced by phycocyanin, along with abnormal morphologic changes. The transcriptome analysis showed that 2970 genes were differentially expressed after phycocyanin treatment in A549 cells, including 1431 down-regulated and 1539 up-regulated genes. Gene ontology and KEGG analysis suggested that some classical pathways, such as Wnt, NF-κB, and PI3K-AKT signaling, were significantly enriched. Strikingly, protein⁻protein interaction (PPI) analysis showed that ubiquitin-C (UBC) occupied the highest degree (the highest number of interactions) in differential genes, indicating that it might play a key role in the phycocyanin-mediated regulatory process in A549 cells. Moreover, qRT-PCR results showed consistent expression trends of differential genes with transcriptome analysis. Consequently, this study has provided a theoretical basis for regulation of phycocyanin in A549 cells, which lays a foundation for the treatment of NSCLC.

As a type of functional food additive, phycocyanin is shown to have a potential antineoplastic property. However, its underlying anticancer mechanism in melanoma cells remains unknown. We previously reported a 35 S in vivo/vitro labeling analysis for dynamic proteomic (SiLAD) technology. It could exclusively detect protein synthesis rates via pulse labeling of newly expressed proteins by 35 S, providing a high time-resolution method for analysis of protein variations. In the present study, we performed a time course analysis in A375 melanoma cells after phycocyanin treatment using SiLAD. Protein expression velocities were specifically visualized and their regulation modes were dynamically traced. Strikingly, novel protein synthesis patterns were discovered in the early phase of phycocyanin treatment, suggesting a possible mechanism of phycocyanin regulation. Furthermore, network analysis and phenotype experiments demonstrated that GRB2-ERK1/2 pathway was involved in phycocyanin-mediated regulation process and responsible for the proliferation suppression of melanoma cell, which could be a therapeutic target for malignant melanoma.

Phycocyanin, a type of functional food colorant, is shown to have a potent anti-cancer property. Non-small cell lung cancer (NSCLC) is one of the most aggressive form of cancers with few effective therapeutic options. Previous studies have demonstrated that phycocyanin exerts a growth inhibitory effect on NSCLC A549 cells. However, its biological function and underlying regulatory mechanism on other cells still remain unknown. Here, we investigated the in vitro function of phycocyanin on three typical NSCLC cell lines, NCI-H1299, NCI-H460, and LTEP-A2, for the first time. The results showed that phycocyanin could significantly induce apoptosis, cell cycle arrest, as well as suppress cell migration, proliferation, and the colony formation ability of NSCLC cells through regulating multiple key genes. Strikingly, phycocyanin was discovered to affect the cell phenotype through regulating the NF-κB signaling of NSCLC cells. Our findings demonstrated the anti-neoplastic function of phycocyanin and provided valuable information for the regulation of phycocyanin in NSCLC cells.

Phycocyanin (PC) is a kind of natural pigment protein complex derived from marine algae. It is also a type of important food functional factor with anti-cancer, anti-inflammatory, and immune -enhancing activities, and has been widely used in functional food, medicine and cosmetics. Phycocyanin has been proven to inhibit the activity of non-small cell lung cancer (NSCLC) cells, but the underlying regulatory mechanism is not fully understood. This study focused on miR-642a-3p, and investigated the potential regulating mechanism of phycocyanin in NSCLC cells. The results showed that phycocyanin upregulated the expression level of miR-642a-3p in four NSCLC cells (A549, H1299, H460 and LTEP-a2). Overexpression of miR-642a-3p levels significantly inhibited the proliferation, migration and unanchored growth of four cells in vitro. In addition, transfection of miRNA inhibitors to interfere with the expression of miR-642a- 3p could enhance cell viability to a certain extent. This study preliminarily revealed that the up-regulation expression of miR-642a-3p was involved in the regulation of inhibiting NSCLC cell viabilities by phycocyanin, which could lay a sci¬entific theoretical basis for the in-depth study and utilization of phycocyanin. [ABSTRACT FROM AUTHOR]

Phycocyanin is a type of marine natural product and functional food additive. Studies have demonstrated that phycocyanin has potential regulatory effects on glycometabolism, while its function and mechanism, especially in type 2 diabetes mellitus (T2DM), is still unclear. The aim of this study was to investigate the antidiabetic roles and underlying mechanism of phycocyanin in a high glucose high fat diet induced model of T2MD in C57BL/6N mice and a high-insulin-induced insulin-resistant model of SMMC-7721 cells. The results indicated that phycocyanin reduced high glucose high fat diet induced hyperglycemia as well as ameliorated glucose tolerance and histological changes in the liver and pancreas. Meanwhile, phycocyanin also significantly decreased the diabetes-induced abnormal serum biomarker variations, including triglyceride (TG), total cholesterol (TC), aspartate transaminase (AST), and glutamic-pyruvic transaminase (ALT), and increased the superoxide dismutase (SOD) content. Furthermore, the antidiabetic function of phycocyanin was exerted through activating the AKT and AMPK signaling pathway in the mouse liver, which was also verified in the insulin-resistant SMMC-7721 cells due to increased glucose uptake and activated AKT and AMPKα expression. Thus, the present study is the first to indicate that phycocyanin mediates antidiabetic function via activating the AKT and AMPK pathway in high glucose high fat diet induced T2DM mice and insulin-resistant SMMC-7721 cells, which lays a scientific theoretical basis for the potential treatment of diabetes and the utilization of marine natural products. [ABSTRACT FROM AUTHOR]

Phycocyanin, a type of marine-derived food pigment protein, has been reported to exhibit multiple biological functions, while the function of its potential bioactive peptides is rarely investigated. Previously, a novel phycocyanin-derived bioactive peptide (PCP3: MFDAFTK) was identified in our study. The aim of this study was to further explore its anti-inflammatory function of small intestine based on both intestinal organoids and mice models. The results revealed that PCP3 could significantly ameliorate the inflammatory symptoms induced by lipopolysaccharide (LPS), as evidenced by the increased intensity and crypt bud numbers of organoids, the decreased levels of inflammatory factor, the promoted expressions of tight junction and intestinal epithelial cell markers, and the reduced oxidative stress levels of organoids. The in vivo experiments also indicated that PCP3 ameliorated LPS-induced small intestinal inflammation in mice through restoring the physiological form of small intestine, as well as intestinal tight junctions. In addition, pathway analysis suggested that Akt and AMPK/autophagy signaling are involved in the improved process of intestinal inflammation mediated by PCP3. Collectively, this study has laid the foundation for the application of phycocyanin and phycocyanin-derived bioactive peptides in the field of intestinal inflammatory disease, and provides a scientific theoretical basis for the amelioration of intestinal inflammation through functional foods and food derivatives. [Display omitted] • PCP3 is discovered as a novel phycocyanin-derived bioactive peptide. • PCP3 exhibits extraordinary anti-inflammatory function in mice. • PCP3 also ameliorates the LPS-induced inflammation of small intestinal organoids. • The impaired tight junctions by inflammation are dramatically restored by PCP3. • Akt and AMPK/autophagy signaling are involved in the regulatory process of PCP3. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is one of the most lethal types of malignancies around the world. Phycocyanin, a type of functional food additive derived from photosynthetic pigment protein in Spirulina cells, has been verified to exhibit antineoplastic effect on NSCLC. However, the investigation on bioactive peptides of phycocyanin, especially in NSCLC, remains poorly documented. The goal of this work is to identify novel phycocyanin-derived bioactive peptides with NSCLC cell inhibition function. Phycocyanin was hydrolysed by trypsin, followed by peptides isolation, purification and identification through ultrafiltration, high performance liquid chromatography (HPLC) and mass spectrometry (MS), respectively. Three phycocyanin peptides (PCP1: AGDASVLEDR, PCP2: ADSLLSGLR and PCP3: MFDAFTK) predicted to exhibiting anticancer ability were identified. Molecular docking analysis indicated the peptides had strong interaction with epidermal growth factor receptor (EGFR), a proto-oncogene in cells. Phenotype experiments showed that peptides significantly inhibited growth and migration of A549, H1299 and LTEP-a2 cells. Moreover, they also suppressed the activity of Akt pathway of NSCLC cells. Three phycocyanin-derived peptides might be suitable for development as new anti-lung cancer agents, owing to their antineoplastic activities. The current work also provides a vital basis for further utilization of marine algae nutrient components. [Display omitted] • Three antineoplastic peptides (PCP1-3) derived from phycocyanin are successfully identified. • Novel peptides are: AGDASVLEDR (PCP1), ADSLLSGLR (PCP2) and MFDAFTK(PCP3). • EGFR exhibits strong docking affinity with PCP1, PCP2 and PCP3. • PCP1-3 significantly inhibits viability and migration of A549 cells in vitro. • The novel bioactive peptides have great development potential in functional field. [ABSTRACT FROM AUTHOR]

[Display omitted] • High level of miR-34a-5p and low level of miR-338-3p are expressed in T2DM cells. • miR-338-3p and miR-34a-5p act as antagonists in the phycocyanin-mediated process of T2DM amelioration. • PTPRM and NR3C2 are direct targets of miR-34a-5p and miR-338-3p, respectively. • miR-34a-5p/Ptprm and miR-338-3p/Nr3c2 axis are involved in phycocyanin-mediated glucose regulating process. Phycocyanin has been demonstrated to regulate glycometabolism. Previously, we discovered phycocyanin could protect against type 2 diabetes mellitus (T2DM), while its mechanism is still unclear. In this work, a miRNA-seq was employed to investigate potential vital miRNAs. The results indicated that miR-338-3p expression was decreased in T2DM, which was rescued by phycocyanin, while the expression of miR-34a-5p showed opposite trend. Knockdown miR-338-3p expression or overexpression of miR-34a-5p both reduced the glucose utilization of cells, while could be significantly reversed by phycocyanin. Dual-luciferase reporter assays suggested that PTPRM and NR3C2 are direct targets of miR-34a-5p and miR-338-3p, respectively. Strikingly, knockdown PTPRM expression impacted the uptake of glucose in normal cells, while interfering NR3C2 expression alleviated the decreased glucose availability caused by insulin resistance (IR). Thus, the present work demonstrated that miR-338-3p and miR-34a-5p act as antagonists in phycocyanin-mediated process of ameliorating glycometabolism, which highlights a critical role of miRNAs in regulating glycometabolism. [ABSTRACT FROM AUTHOR]

[Display omitted] • LINC00852 expression is suppressed by phycocyanin in NSCLC cells. • LINC00852 acts as a ceRNA of miR-29a-3p which further targets LAMTOR1 gene. • Phycocyanin inhibits NSCLC vitality through LINC00852/miR-29a-3p/LAMTOR1 axis. • AMPK activation is involved in the above axis-mediated inhibition in NSCLC cells. Phycocyanin has been reported to exert antineoplastic function in non-small cell lung cancer (NSCLC), while the underlying molecular mechanism is still largely unclear. In this study, a whole transcriptome resequencing was employed. Results showed that lncRNA LINC00852 was inhibited by phycocyanin in NSCLC cells. Knockdown LINC00852 expression resulted in the attenuated proliferation, viability and migration ability of NSCLC cells. Meanwhile, dual-luciferase reporter assay indicated that LINC00852 acted as a ceRNA of miR-29a-3p which further targets regulator complex protein LAMTOR1 (LAMTOR1). Overexpression miR-29a-3p or knockdown LAMTOR1 expression decreased the activity of NSCLC cells, respectively. Moreover, AMPK signaling was activated upon LINC00852 knockdown, miR-29a-3p enhancement or LAMTOR1 inhibition, which was in consistent with the phycocyanin exposure results. In summary, we demonstrated that LINC00852 played a key role in phycocyanin-mediated NSCLC regulation process, and the epigenetic signaling LINC00852/miR-29a-3p/LAMTOR1 may be considered as novel molecular targets for fighting NSCLC base on marine functional foods. [ABSTRACT FROM AUTHOR]

[Display omitted] • Phycocyanin inhibits the growth of NSCLC cells. • Phycocyanin induces autophagy and autophagy flux in NSCLC cells. • AMPK signaling pathway activation is involved in phycocyanin-treated lung cancer cells. • Phycocyanin attenuated viability of multiple lung cancer cells through promoting autophagy. Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide. Phycocyanin, a type of marine food additives, has been reported to exert antineoplastic effects in NSCLC. The aim of this study was to investigate roles of autophagy in the anticancer process of phycocyanin in NSCLC. Results showed that phycocyanin increased LC3-II/LC3-I ratio and decreased p62 level of NSCLC cells in a dose- and time-dependent manner. Laser scanning confocal observation of autophagic LC3 puncta showed phycocyanin promotes autophagy flux of NSCLC cells. In addition, AMPK signaling was activated upon phycocyanin treatment. Strikingly, phycocyanin was shown to synergistically affect the autophagy of cells with rapamycin and chloroquine, thus concertedly inhibiting the viabilities of NSCLC cells. These results indicated that the antineoplastic effect of phycocyanin could be attributed to the activated autophagy and AMPK signaling pathway. Thus, targeting autophagy could be a promising way to improve NSCLC though phycocyanin. [ABSTRACT FROM AUTHOR]

[Display omitted] • Phycocyanin diminishes the viability of A549 cells. • Phycocyanin significantly promotes expressions of miR-3150a-3p, miR-6883-3p and miR-627-5p. • TIRAP is a shared directed target of miR-3150a-3p, miR-6883-3p and miR-627-5p. • Knockdown TIRAP expression resulted in similar cell phenotype as miRNAs overexpression. • Overexpression TIRAP restores the diminished A549 viability caused by miRNAs and phycocyanin. As a type of functional food additives, phycocyanin is well-known for its extraordinary antineoplastic activity in non-small cell lung cancer (NSCLC). Previously, a high-throughput miRNA sequencing was employed to excavate miRNAs altered by phycocyanin in A549 cells, while the in-depth regulatory mechanism was inadequate. In this work, three significant up-regulated miRNAs in phycocyanin-treated cells are identified for the first time, including miR-3150a-3p, miR-6883-3p and miR-627-5p. Overexpression of miRNAs obviously diminished the cell growth and colony formation capacity, respectively. Dual-luciferase reporter assay verified that toll/interleukin 1 receptor domain-containing adaptor protein (TIRAP) was a direct shared target of three miRNAs. Knockdown the expression of TIRAP resulted in similar cell growth inhibition phenotype as miRNAs overexpression. Strikingly, overexpression of TIRAP could significantly restore the diminished cell viability caused by miRNAs up-regulation, as well as phycocyanin treatment. Consequently, this study proposes that phycocyanin plays an inhibitory effect of NSCLC cells via a miR-3150a-3p/miR-6883-3p/miR-627-5p-TIRAP axis. [ABSTRACT FROM AUTHOR]

[Display omitted] • miRNA variations were screened through high-throughput miRNA-seq. • miR-642a-5p was significantly increased by phycocyanin in NSCLC cells. • RIPK1 was a direct target of miR-642a-5p in NSCLC cells. • Phycocyanin inhibits NSCLC cell activities through miR-642a-5p/RIPK1/NF-κB axis. Phycocyanin, a type of functional food additive, is shown to exert antineoplastic property in non-small cell lung cancer (NSCLC). Our previous work demonstrated that phycocyanin could suppress the viability of NSCLC cells via regulating receptor-interacting serine/threonine-protein kinase 1 (RIPK1), but the underlying mechanism remains unknown. Herein, a high-throughput miRNA sequencing method was employed to further explore miRNA variations for the first time. 43 down-regulated and 18 up-regulated miRNAs displayed differential expressions after phycocyanin exposure. Particularly, the expression of miR-642a-5p was significantly increased by phycocyanin. Dual-luciferase assay revealed that RIPK1 was a direct target of miR-642a-5p. siRNA knockdown RIPK1 expression and overexpression of miR-642a-5p both inhibited cell proliferation, colony formation and NF-κB activity, as well as induced apoptosis of NSCLC cells. The anticancer effect of phycocyanin was also validated in vivo using subcutaneous tumor formation model in nude mice. This study proposes that phycocyanin inhibits NSCLC cell activities through miR-642a-5p/RIPK1/NF-κB axis. [ABSTRACT FROM AUTHOR]

• Phycocyanin exerts anticancer functions through miRNAs participating. • Expressions of multiple miRNAs were altered by phycocyanin in NSCLC cells. • A "targets interaction" network was established in phycocyanin regulating process. • miR-1249-5p, miR-1231, miR-547-5p, and miR-93-5p may played key roles. • Targeting key miRNAs regulated by phycocyanin contributes to treatment of NSCLC. Phycocyanin is a type of marine functional food additive, exerting good antitumor property. However, its antineoplastic mechanism in non-small cell lung cancer (NSCLC) remains unclear. In this work, a high-throughput micro-RNA sequencing was employed to analyze key miRNAs regulated by phycocyanin in A549 cells for the first time. Results showed that a total of 61 miRNAs were differentially expressed between control and phycocyanin-treated cells, including 18 up-regulated and 43 down-regulated miRNAs. Subsequently, 483 validated target genes were predicted. Strikingly, protein–protein interaction analysis showed that target genes like EGFR, CDK2, POLR2E, TP53, and MED28 occupied high degrees in networks, which were predicted regulated by miR-1249-5p, miR-1231, miR-547-5p, and miR-93-5p. Furthermore, qRT-PCR showed strong consistent expression trends of differential miRNAs with miRNA-seq results. Consequently, this study significantly advances our understanding of the regulatory mechanisms of phycocyanin, especially with regard to miRNAs, and also lays a theoretical foundation for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]