Modified natriuretic peptides and their potential roles in cancer treatment

Liu, Xingzhu; Li, Ping; Yang, Yadong; Zhang, Wenyuan; Zhao, Siyu; Zeng, Ying; Zhou, Xile; Zeng, Ling‐Hui; Yang, Geng

doi:10.1016/j.bj.2021.06.007

Cited by 13 publications

(16 citation statements)

References 88 publications

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“…The NP families, mainly including A-type natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), are well known produced in the cardiovascular and central nervous systems ( 4 ). They play important roles in cardioprotective function, regulation of blood pressure, fluid balance, and follicles development ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

C-Type Natriuretic Peptide Regulates the Expression and Secretion of Antibacterial Peptide S100A7 in Goat Mammary Gland Through PKG/JNK/c-Jun Signaling Pathway

et al. 2022

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During infection, the infected tissue secretes a variety of endogenous peptides to resist further invasion of pathogens. Among these endogenous peptides, the natriuretic peptides and the antimicrobial peptides attracted the most attention. C-type natriuretic peptide (CNP) and its receptor natriuretic peptide receptor B (NPR-B) were members of the natriuretic peptide system. The antimicrobial peptide S100A7 plays an important role to resist infection of bacteria in mastitis. It is reported that the expression of S100A7 is regulated by an activator protein-1 (AP-1)-responsive promoter. As a subunit of AP-1, c-Jun is a downstream target of CNP/NPR-B signaling pathway. Therefore, it is a hypothesis that the CNP/NPR-B signaling pathway induces the expression and secretion of S100A7 in mammary glands to take part in local mammary gland innate immunity. To verify this hypothesis, goat mammary gland and isolated mammary epithelial cells (MECs) were used to explore the expression of CNP/NPR-B and their physiological roles in goat mammary gland. The results showed that goat mammary gland expressed NPR-B, but not CNP. The expression and secretion of S100A7 in goat MECs were obviously induced by CNP/NPR-B signaling pathway. After treatment with CNP, the cyclic guanosine monophosphate (cGMP) level in goat MECs was significantly upregulated. Along with the upregulation of cGMP level, the phosphorylation levels of c-Jun N-terminal kinase (JNK) and its target c-Jun were also increased gradually. KT5823 is a specific inhibitor for protein kinase G (PKG). KT5823 remarkably inhibited the phosphorylation of JNK and c-Jun induced by CNP. Correspondingly, KT5823 evidently inhibited the expression and secretion of S100A7 induced by CNP. On the other hand, the expression of NPR-B and S100A7 was upregulated in the mastitis goat mammary gland. But, there was no significant difference in expression of CNP between healthy and mastitis goat mammary gland tissues. The goat mastitis model was established in vitro using goat MECs treated by lipopolysaccharide (LPS). LPS treatment also could increase the expression of NPR-B and S100A7. In conclusion, goat mammary gland expressed NPR-B, indicating mammary gland was the target organ for natriuretic peptide system. Moreover, CNP, through NPR-B/JNK/c-Jun signaling pathway to regulate the expression and secretion of S100A7 in MECs, played an important role in mammary gland innate immunity.

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Section: Introductionmentioning

confidence: 99%

C-Type Natriuretic Peptide Regulates the Expression and Secretion of Antibacterial Peptide S100A7 in Goat Mammary Gland Through PKG/JNK/c-Jun Signaling Pathway

et al. 2022

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“…However, modified peptides in which the amino acids (AAs) always were artificially modified, could be more suitable for cancer vaccines, especially for melanoma immunotherapy ( 65 , 67 , 79 , 99 , 110 , 118 , 147 ) ( Figure 3 ). The reason modified peptides are more effective may be because the AAs of modified peptides are altered and these modified peptides will be treated as exogenous peptides, which are more easily recognized by T cells and therefore more immunogenic ( 12 , 203 – 205 ). Alternatively, the genes of these modified peptides are always expressed or overexpressed in tumor cells ( Figure S1 ), and their comparative wild-type peptides are usually known to have binding affinities for certain HLA alleles ( 206 – 208 ).…”

Section: Discussionmentioning

confidence: 99%

Potential association factors for developing effective peptide-based cancer vaccines

et al. 2022

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Peptide-based cancer vaccines have been shown to boost immune systems to kill tumor cells in cancer patients. However, designing an effective T cell epitope peptide-based cancer vaccine still remains a challenge and is a major hurdle for the application of cancer vaccines. In this study, we constructed for the first time a library of peptide-based cancer vaccines and their clinical attributes, named CancerVaccine (https://peptidecancervaccine.weebly.com/). To investigate the association factors that influence the effectiveness of cancer vaccines, these peptide-based cancer vaccines were classified into high (HCR) and low (LCR) clinical responses based on their clinical efficacy. Our study highlights that modified peptides derived from artificially modified proteins are suitable as cancer vaccines, especially for melanoma. It may be possible to advance cancer vaccines by screening for HLA class II affinity peptides may be an effective therapeutic strategy. In addition, the treatment regimen has the potential to influence the clinical response of a cancer vaccine, and Montanide ISA-51 might be an effective adjuvant. Finally, we constructed a high sensitivity and specificity machine learning model to assist in designing peptide-based cancer vaccines capable of providing high clinical responses. Together, our findings illustrate that a high clinical response following peptide-based cancer vaccination is correlated with the right type of peptide, the appropriate adjuvant, and a matched HLA allele, as well as an appropriate treatment regimen. This study would allow for enhanced development of cancer vaccines.

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“…In this study, we found that the < 5 kDa CCP showed good anti-tumor activity. A lot of anti-tumor peptides have been found in recent years because of their advantages of targeting, specificity, safety, and so on ( 57 , 58 ). The anti-tumor mechanisms of these peptides are diversified: direct anti-tumor effect can be achieved by inhibiting the proliferation of tumor cells and promoting the apoptosis of tumor cells, or indirect anti-tumor effect can be achieved by enhancing and stimulating the immune response of the body to tumor cells, or by inhibiting the formation of tumor blood vessels ( 58 , 59 ).…”

Section: Discussionmentioning

confidence: 99%

“…A lot of anti-tumor peptides have been found in recent years because of their advantages of targeting, specificity, safety, and so on ( 57 , 58 ). The anti-tumor mechanisms of these peptides are diversified: direct anti-tumor effect can be achieved by inhibiting the proliferation of tumor cells and promoting the apoptosis of tumor cells, or indirect anti-tumor effect can be achieved by enhancing and stimulating the immune response of the body to tumor cells, or by inhibiting the formation of tumor blood vessels ( 58 , 59 ). Besides, many studies have demonstrated that the anti-tumor effect of zinc could be potentially due to its differential regulation of host immune cells and cancer cells within the tumor microenvironment ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Chicken skin-derived collagen peptides chelated zinc promotes zinc absorption and represses tumor growth and invasion in vivo by suppressing autophagy

Liu

Zou²,

Ji³

et al. 2022

Front. Nutr.

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To improve the utilization value of chicken by-products, we utilized the method of step-by-step hydrolysis with bromelain and flavourzyme to prepare low molecular weight chicken skin collagen peptides (CCP) (<5 kDa) and characterized the amino acids composition of the CCP. Then, we prepared novel CCP-chelated zinc (CCP–Zn) by chelating the CCP with ZnSO4. We found that the bioavailability of CCP–Zn is higher than ZnSO4. Besides, CCP, ZnSO4, or CCP–Zn effectively repressed the tumor growth, invasion, and migration in a Drosophila malignant tumor model. Moreover, the anti-tumor activity of CCP–Zn is higher than CCP or ZnSO4. Furthermore, the functional mechanism studies indicated that CCP, ZnSO4, or CCP–Zn inhibits tumor progression by reducing the autonomous and non-autonomous autophagy in tumor cells and the microenvironment. Therefore, this research provides in vivo evidence for utilizing chicken skin in the development of zinc supplements and cancer treatment in the future.

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Modified natriuretic peptides and their potential roles in cancer treatment

Cited by 13 publications

References 88 publications

C-Type Natriuretic Peptide Regulates the Expression and Secretion of Antibacterial Peptide S100A7 in Goat Mammary Gland Through PKG/JNK/c-Jun Signaling Pathway

C-Type Natriuretic Peptide Regulates the Expression and Secretion of Antibacterial Peptide S100A7 in Goat Mammary Gland Through PKG/JNK/c-Jun Signaling Pathway

Potential association factors for developing effective peptide-based cancer vaccines

Chicken skin-derived collagen peptides chelated zinc promotes zinc absorption and represses tumor growth and invasion in vivo by suppressing autophagy

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