Targeted Ablation of Prostate Carcinoma Cells Through LH Receptor Using Hecate-CGβ Conjugate: Functional Characteristic and Molecular Mechanism of Cell Death Pathway

Bodek, Gabriel; Kowalczyk, Anna; Wacławik, Agnieszka; Huhtaniemi, Ilpo; Ziȩcik, Adam J.

doi:10.1177/15353702-0323006-10

Cited by 17 publications

(9 citation statements)

References 24 publications

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“…This plausible given the rapid mode of action that was observed during the real-time images and trypan blue staining, confirming near 80% cell death after only 6hr of treatment and near 100% cell death after the 24h period. Furthermore this is supported by previous reports utilizing lytic peptides for cancer, that suggest that necrosis is main mode of action compared to apoptosis [26]. Regardless of the mechanism of action, both peptides appeared to cause significant tumor-specific cell death.…”

Section: Discussionsupporting

confidence: 83%

“…To achieve this, two 33-amino acid peptide sequences, designated JCH and JC21, were synthesized (Figure 1A). Since LHRH-R over-expression is associated with aggressive prostate cancers [7, 26–28], a modified LHRH 10-amino acid sequence (QHWSYGLRP), was utilized for selective targeting, with a single amino acid modification (QHWSWGLRP) to increase hydrophobicity and enhance anti-tumor activity while limiting this activity on non-cancerous cells (Figure 1B). …”

Section: Resultsmentioning

confidence: 99%

“…LHRH-conjugated lytic peptides target the LHRH receptors of prostate cancer cells [6, 7, 26, 28, 33]. In the present study, new lytic peptide sequences and a new LHRH sequence, modified from the full-length LHRH sequence, were utilized to target and destroy androgen-dependent and androgen-independent prostate cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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LHRH-conjugated lytic peptides directly target prostate cancer cells

Yates

Sharp

Jones

et al. 2011

Biochemical Pharmacology

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Prostate cancer is the second leading cause of cancer deaths among men. For patients with hormone-refractory disease, few treatments are available once the tumor has metastasized beyond the prostate. In the present study, two conjugated lytic peptide sequences (named JCHLHRH and JC21LHRH) were designed to target luteinizing hormone-releasing hormone receptors (LHRH-R). Our results indicate that human prostate cancer cell lines were sensitive to both LHRH-conjugated and non-conjugated lytic peptides, with IC 50 concentrations for LNCaP cells, 4.4 and 9.1 µM; for DU-145 cells, 4.8 and 5.7 µM; and for PC-3 cells, 4.4 and 8.2 µM, respectively. JCHLHRH and JC21LHRH were nontoxic to normal primary human prostate epithelial cells or to bone marrow stromal cells in co-culture. There were morphological changes in PC-3 cells after 3 hr of exposure to either peptide; after 6 hr, there were significant reductions in cell numbers. Exposure of PC-3 cells for 24 hr to either JCHLHRH or JC21LHRH blocked their growth over 3 days. Since JCHLHRH and JC21LHRH have specificity for and anti-proliferative activity against tumor cells, and low toxicity for normal prostate cells, these peptides could serve as a new type of therapy for prostate cancer.

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Section: Discussionsupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

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LHRH-conjugated lytic peptides directly target prostate cancer cells

Yates

Sharp

Jones

et al. 2011

Biochemical Pharmacology

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“…No changes in body weight or histological abnormalities were found in any of the organs examined, except the testes. These interesting findings were also noticed by Bodek et al [12] who found that a Hecate-CGbeta conjugate (lytic peptide and ␤ -chorionic gonadotropin) selectively destroyed cells possessing LH receptors. The authors described the functional characteristics of the conjugate and the molecular mechanism of the cell death pathway in prostate cancer cells.…”

Section: Lh and Prostate Cancersupporting

confidence: 72%

Gonadotropins and Prostate Cancer – Revisited

Thwaini

Naase²,

Chinegwundoh

et al. 2006

Urol Int

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Luteinizing hormone and follicle-stimulating hormone are called gonadotropins, because they stimulate the gonads – in males the testes and in females the ovaries. They are not necessary for life, but are essential for reproduction. In addition, the association of these hormones with prostate cancer has been the interest of many researchers. Their detection in the human prostate has been investigated using different methods, including immunologic and RT-PCR techniques. In addition, the increasing evidence of paracrine/autocrine functions of the gonadotropic glycoprotein hormones, their allocation to the superfamily of cystine knot growth factors, and luteinizing hormone/chorionic gonadotropin receptor gene expression in non-gonadal tissues led many researchers to investigate intraprostatic glycoprotein hormones and their receptor gene expression. We aim in this review to shed light on the physiology of the gonadotropins and their association with prostate cancer and highlight the future possibilities of their use as targets in treating this disease.

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“…We have investigated in vitro the susceptibility of various gonadal and non-gonadal cancer cell types, expressing and non-expressing LH/hCG receptors, to Hecate-CGβ conjugate treatment (Zaleska et al, 2003;Bodek et al, 2003Bodek et al, , 2005a. In a dose-and timedependent manner, the conjugate selectively destroyed cells possessing LH/hCG in lower concentrations than Hecate alone and the efficacy strongly correlate with the number of LH/hCG receptors.…”

Section: Targeted Treatment Of the Gonadal And Non-gonadal Tumors Thrmentioning

confidence: 99%

Novel biological and possible applicable roles of LH/hCG receptor

Ziȩcik

Kaczmarek

Blitek

et al. 2007

Molecular and Cellular Endocrinology

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Luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors are widely expressed in gonadal cells, however, the presence of these receptors has also been demonstrated in several other non-gonadal female and male tissues. The expression level of non-gonadal LH/hCG receptors is much lower than in gonads, although their expression is regulated by similar mechanisms and they also exert biological effects using similar signaling pathways. Hormonally regulated LH/hCG receptor expression in the oviduct suggests that LH could be involved in the regulation of its contraction, gametes/embryos transport and synchronization of the fertilization. One of the major roles of the myometrial LH/hCG receptors may also be the stimulation of growth and maintenance of the uterine relaxation during pregnancy. In pigs, LH seems to be one of the pleiotropic factors which influence the endometrial prostaglandin F(2alpha) synthesis and initiation of the luteolysis. The LH/hCG receptor expression in several cancer cells provides new possibilities for developing new strategies for targeted cancer therapy based on lytic LH/hCG conjugates.

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Targeted Ablation of Prostate Carcinoma Cells Through LH Receptor Using Hecate-CGβ Conjugate: Functional Characteristic and Molecular Mechanism of Cell Death Pathway

Cited by 17 publications

References 24 publications

LHRH-conjugated lytic peptides directly target prostate cancer cells

LHRH-conjugated lytic peptides directly target prostate cancer cells

Gonadotropins and Prostate Cancer – Revisited

Novel biological and possible applicable roles of LH/hCG receptor

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