Use of hecate–chorionic gonadotropin β conjugate in therapy of lutenizing hormone receptor expressing gonadal somatic cell tumors

Rivero-Müller, Adolfo; Vuorenoja, Susanna; Tuominen, M.; Wacławik, Agnieszka; Brokken, Leon J. S.; Ziȩcik, Adam J.; Huhtaniemi, Ilpo; Rahman, Nafis

doi:10.1016/j.mce.2006.11.016

Cited by 16 publications

(11 citation statements)

References 59 publications

(54 reference statements)

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“…The effect of Diptericin is restricted to the tumor cells and does not extend to normal cells. A hypothesis has been proposed in which AMPs have a higher affinity against tumor cells than against normal cells because of a difference in electric charge on the plasma membrane (Rivero-Muller et al, 2007). Some tumor cells have a net negative charge on the plasma membrane, similar to bacterial cells.…”

Section: Discussionmentioning

confidence: 99%

“…However, a mechanism for this induction has not yet been established. It has been argued that AMPs bind to tumor cell membranes via an electrostatic interaction and align themselves parallel to the membrane surface (Rivero-Muller et al, 2007). After enough peptide molecules have assembled on the membrane surface, they permeate the membrane, which is followed by membrane disintegration and micellization.…”

Section: Discussionmentioning

confidence: 99%

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Anti-tumor effects of antimicrobial peptides, targets of the innate immune system, against hematopoietic tumors inDrosophila mxcmutants

Araki

Awane

Sato³

et al. 2018

Preprint

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The innate immune response is the first line of defense against microbial infections. In Drosophila, three immune pathways induce the synthesis of antimicrobial peptides (AMPs) in the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells. However, little is known about their anti-tumor effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval hematopoietic organ called the lymph gland (LG). Here, using RNA-Seq analysis, we found that many immunoresponsive genes, including AMP genes, were up-regulated in the mutants. Down-regulation of these pathways by either a Toll or an imd mutation enhanced the tumor phenotype of the mxc mutants. Conversely, ectopic expression of each of five different AMPs in the fat body significantly suppressed the LG hyperplasia phenotype in the mutants. Thus, we propose that the Drosophila innate immune system can suppress progression of hematopoietic tumors by inducing AMP gene expression. Overexpression of any one of these five AMPs resulted in enhanced apoptosis in the mutant LGs, while no apoptosis signals were detected in controls. We observed that two AMPs, Drosomycin and Defensin, were taken up by circulating hemocyte-like cells, which were associated with LG regions showing reduced cell-to-cell adhesion in the mutants; another AMP, diptericin, was directly localized on the tumors without intermediating hemocytes. These results lead us to conclude that the AMPs have a specific cytotoxic effect that enhance apoptosis exclusively in the tumor cells.Summary statement:Antimicrobial peptides can be associated with tumor cells generated in a hematopoietic tissue in Drosophila mxc mutants and have an anti-tumor effect in suppressing their growth.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Anti-tumor effects of antimicrobial peptides, targets of the innate immune system, against hematopoietic tumors inDrosophila mxcmutants

Araki

Awane

Sato³

et al. 2018

Preprint

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“…After binding, they can generate physical holes causing leakage of the cell content and, finally, cell death [ 118 ]. To further improve their selectivity and to reduce side effects to healthy cells, Rivero-Mueller et al generated a peptide conjugate composed of an AMP and a cancer-targeting peptide [ 60 ]. Such hybrid peptides including a targeting domain and a cell-killing domain are usually obtained by direct chemical peptide synthesis or as fusion protein expressed in a recombinant system.…”

Section: Modified Amps and Amp Conjugatesmentioning

confidence: 99%

Design and Application of Antimicrobial Peptide Conjugates

Reinhardt

Neundorf

2016

IJMS

120

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Antimicrobial peptides (AMPs) are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT) or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry.

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“…Hecate is an analogue of the main component of bee venom melittin which preferentially kills the cancer cells. This peptide was already conjugated with β chorionic gonadotropin fragments and tested with promising effects in the case of cancers expressing LH/HCG receptors [34][35][36][37]. However, this possibility should be limited by the risk of the stable destruction of non-neoplastic tissues expressing FSHR, like zona granulosa of the ovary in premenopausal women or Sertoli cells in the male testis.…”

Section: Fshr Inhibition or Destruction And Their Possible Role In Fsmentioning

confidence: 99%

Ekspresja receptorów hormonu dojrzewania pęcherzyków w naczyniach wewnątrzguzowych i komórkach nowotworowych — udział w progresji guzów i perspektywy zastosowania w diagnozie i terapii raka

Łódź

2018

Endokrynologia Polska

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In normal conditions follicle stimulating hormone receptors (FSHR) are expressed in zona granulosa cells of the ovary and Sertoli cells of the testis. However, the ectopic expression of FSHR was recently discovered in intra-tumoral blood vessels endothelia and/or in tumoral cells of many extra-gonadal human tumors (particularly in endocrine tumours). The paper reviews the data concerning the appearance of ectopic FSHR in particular human neoplasms. The possible involvement of FSHR in tumor progression and the use of FSHR examination for diagnostic purposes is also reviewed. Finally, the putative role of FSHR as a new target in oncological therapy is also discussed.

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Use of hecate–chorionic gonadotropin β conjugate in therapy of lutenizing hormone receptor expressing gonadal somatic cell tumors

Cited by 16 publications

References 59 publications

Anti-tumor effects of antimicrobial peptides, targets of the innate immune system, against hematopoietic tumors inDrosophila mxcmutants

Anti-tumor effects of antimicrobial peptides, targets of the innate immune system, against hematopoietic tumors inDrosophila mxcmutants

Design and Application of Antimicrobial Peptide Conjugates

Ekspresja receptorów hormonu dojrzewania pęcherzyków w naczyniach wewnątrzguzowych i komórkach nowotworowych — udział w progresji guzów i perspektywy zastosowania w diagnozie i terapii raka

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