Bombesin marine toxin conjugates inhibit the growth of lung cancer cells

Moody, Terry W.; Pradhan, Tapas K.; Mantey, Samuel A.; Jensen, Robert T.; Dyba, Marcin; Moody, Deborah L.; Tarasova, Nadya I.; Michejda, Christopher J.

doi:10.1016/j.lfs.2008.01.019

Cited by 19 publications

(16 citation statements)

References 29 publications

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“…These include coupling various BnR-ligands(primarily agonists) to cytotoxic-radioisotopes( 90 Y, 177 Lu)[16•,82,83]; the coupling of BnR-ligands to phthalocyanine or to porphyrin-photosensitizers[84] to allow photodynamic therapy[85]; the coupling to various siRNA which can affect tumor proliferation/growth/viability[35,86]; coupling to various cytotoxic-chemotherapeutic agents including paclitaxel[87], camptothecin[88,89], and doxorubicin[32,90], as well as to various cytotoxic-marine toxins[hemiasterlin,dolastatin][91]; coupling BnR-agonists to the antimicrobial peptide, magainin 11[92] markedly increase the cytotoxiticity of magainin 11 both in vitro in a number of GRPR-containing tumor cells and in vivo in MCF-7- breast-cancer-cells; and coupling BnR-agonists coupled to antimicrobial cytotoxic-peptides showed enhanced cytotoxicity for breast-cancer-cells[93]. A doxorubicin-containing Bn-conjugated-analogue, AN-215,has been studied in a number of different cancers and shown to have antitumor activity in cancers of the pancreas, lung, prostate, colon, ovary, endometrium, breast,stomach,and CNS(glioblastomas)[16•,32].…”

Section: Imaging and Targeted-delivery Of Cytotoxic-agents To Neopmentioning

confidence: 99%

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

Moreno

Ramos-Álvarez

Moody

et al. 2016

Expert Opinion on Therapeutic Targets

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101

102

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Introduction Despite remarkable advances in tumor treatment, many patients still die from common tumors (breast, prostate, lung, CNS, colon, and pancreas), and thus, new approaches are needed. Many of these tumors synthesize bombesin (Bn)-related peptides and over-express their receptors (BnRs), hence functioning as autocrine-growth-factors. Recent studies support the conclusion that Bn-peptides/BnRs are well-positioned for numerous novel antitumor treatments, including interrupting autocrine-growth via the use of over-expressed receptors for imaging and targeting cytotoxic-compounds, either by direct-coupling or combined with nanoparticle-technology. Areas covered The unique ability of common neoplasms to synthesize, secrete, and show a growth/proliferative/differentiating response due to BnR over-expression, is reviewed, both in general and with regard to the most frequently investigated neoplasms (breast, prostate, lung, and CNS). Particular attention is paid to advances in the recent years. Also considered are the possible therapeutic approaches to the growth/differentiation effect of Bn-peptides, as well as the therapeutic implication of the frequent BnR over-expression for tumor-imaging and/or targeted-delivery. Expert opinion Given that Bn-related-peptides/BnRs are so frequently ectopically-expressed by common tumors, which are often malignant and become refractory to conventional treatments, therapeutic interventions using novel approaches to Bn-peptides and receptors are being explored. Of particular interest is the potential of reproducing BnRs in common tumors, such as the recent success of utilizing overexpression of somatostatin-receptors by neuroendocrine-tumors to provide the most sensitive imaging methods and targeted delivery of cytotoxic-compounds.

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Section: Imaging and Targeted-delivery Of Cytotoxic-agents To Neopmentioning

confidence: 99%

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

Moreno

Ramos-Álvarez

Moody

et al. 2016

Expert Opinion on Therapeutic Targets

Self Cite

101

102

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“…The former include coupling Bn analogues to iron oxide nanoparticles for enhancing sensitivity of magnetic resonance imaging [125,204], to various fluorescent molecules which can be used for in vivo imaging [41,173,187,222] or to nanorods containing a photoacoustic imaging moieties [108]. Potentially cytotoxic compounds include coupling Bn analogues to chemotherapeutic agents [camptothecin [88,227,232], doxorubicin [240,241,258], paclitaxel [303,304]]; marine toxins [230]; to diphtheria toxin [360]; to mitochondria-disruptive peptides [40]; to agents that activate polyclonal T lymphocytes [398]; coupled to other immunotherapeutic agents that lead to cell death [48,49]; to photosensitizers [73,73,236,282] and to siRNA or adenoviral delivery vectors[116,242,308,374,375,375]. In addition BnR agonists have been one of the main targeting agents coupled to various nanoparticle carriers to assess delivery [44,342] or for targeted delivery of various cytotoxic agents including chemotherapeutic agents [docataxel [157], doxorubicin [1,3]]; radiolabeled analogues [140]; or gold nanoparticles [45].…”

Section: Bnr Function In Disease and A Therapeutic Target (Table 3)mentioning

confidence: 99%

Insights into bombesin receptors and ligands: Highlighting recent advances

et al. 2015

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This following article is written for Prof. Abba Kastin’s Festschrift, to add to the tribute to his important role in the advancement of the role of peptides in physiological, as well as pathophysiological processes. There have been many advances during the 35 years of his prominent role in the Peptide field, not only as editor of the journal Peptides, but also as a scientific investigator and editor of two volumes of the Handbook of Biological Active Peptides [146,147]. Similar to the advances with many different peptides, during this 35 year period, there have been much progress made in the understanding of the pharmacology, cell biology and the role of (Bombesin) Bn receptors and their ligands in various disease states, since the original isolation of bombesin from skin of the European frog Bombina bombina in 1970 [76]. This paper will briefly review some of these advances over the time period of Prof Kastin 35 years in the peptide field concentrating on the advances since 2007 when many of the results from earlier studies were summarized [128,129]. It is appropriate to do this because there have been 280 articles published in Peptides during this time on Bombesin-related peptides and it accounts for almost 5% of all publications. Furthermore, 22 Bn publications we have been involved in have been published in either Peptides [14,39,55,58,81,92,93,119,152,216,225,226,231,280,302,309,355,361,362] or in the Prof Kastin’s Handbook of Biological Active Peptides [137,138,331].

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“…These results suggest that many of the effects of Bn may be mediated by the EGFR. The marine toxins hemiasterlin (Hem) and dolastatin (Dol) were coupled to a universal Bn agonist using an amide linkage [33]. The resulting Hem-LA-BA1 inhibited specific binding to NCI-H1299 lung cancer with an IC 50 value of 15 nM [Analog #6, Table 12].…”

Section: Review Of Human Radiolabeled Studies Of Bn Receptor-medimentioning

confidence: 99%

“…Hem-LA-BA1 was an agonist, which elevated cytosolic Ca 2+ after addition to lung cancer cells. Hem-LA-BA1, but not BA1 inhibited the proliferation of NCI-H1299 cells in vitro [33]. The results indicate that marine toxin Bn conjugates kill cancer cells enriched in GRP receptors in vitro [33].…”

Section: Review Of Human Radiolabeled Studies Of Bn Receptor-medimentioning

confidence: 99%

“…Hem-LA-BA1, but not BA1 inhibited the proliferation of NCI-H1299 cells in vitro [33]. The results indicate that marine toxin Bn conjugates kill cancer cells enriched in GRP receptors in vitro [33]. It remains to be determined if Hem-LA-BA1 inhibits lung cancer growth in vivo .…”

Section: Review Of Human Radiolabeled Studies Of Bn Receptor-medimentioning

confidence: 99%

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Bombesin Receptor-Mediated Imaging and Cytotoxicity: Review and Current Status

Sancho

Florio²,

Moody³

et al. 2011

CDD

135

209

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The three mammalian bombesin (Bn) receptors (gastrin-releasing peptide [GRP] receptor, neuromedin B [NMB] receptor, BRS-3) are one of the classes of G protein-coupled receptors that are most frequently over-express/ectopically expressed by common, important malignancies. Because of the clinical success of somatostatin receptor-mediated imaging and cytotoxicity with neuroendocrine tumors, there is now increasing interest in pursuing a similar approach with Bn receptors. In the last few years then have been more than 200 studies in this area. In the present paper, the in vitro and in vivo results, as well as results of human studies from many of these studies are reviewed and the current state of Bn receptor-mediated imaging or cytotoxicity is discussed. Both Bn receptor-mediated imaging studies as well as Bn receptor-mediated tumoral cytotoxic studies using radioactive and non-radioactive Bn-based ligands are covered. Keywordsbombesin; gastrin-releasing peptide; neuromedin B; BRS-3; receptor-mediated imaging; tumor cytotoxicity; DOTA; DTPA; NOTA I. Bombesin (Bn) receptor family-General (Table 1,2)The mammalian Bn receptor family is receiving increased attention as a means of localizing tumors or other disease processes by receptor-mediated imaging or for receptor-mediated cytotoxicity of tumors [1][2][3][4][5]. This family got its unusual name, because the original members of this peptide family were isolated from various frog skins and were named after the frog they were isolated from, with the original amidated tetradecapeptide isolated from the European frog, Bombina bombina in 1970 [6][7][8] (Table 2). Subsequently, a large number of related peptides were isolated which were divided into three groups: the Bn-related peptides with a COOH terminal, Gly-His-Leu-Met-NH 2 , the ranatesin-litorin group with a COOH terminus of Gly-His-Phe-Met-NH 2 and the phyllolitorin group with a COOH terminus ending in Gly-Ser-Phe/Leu-Met-NH 2 (Table 2) [6][7][8]. Subsequently two mammalian equivalent peptides were isolated, gastrin-releasing peptide (GRP), a 27 amino Corresponding author: Dr R.T. Jensen, Building 10, Room 9C-103, National Institutes of Health, Bethesda, MD 20892, Phone-301-496-4201, Fax-301-402-0600, robertj@bdg10.niddk.nih.gov. * Both authors contributed equally to this work Conflict of Interest: None NIH Public Access Author ManuscriptCurr Drug Deliv. Author manuscript; available in PMC 2012 January 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript acid peptide which shares the same seven COOH terminal amino acids with Bn (Table 2) [9] and the decapeptide, neuromedin B (NMB) (Tables 1,2) which shares 6 of the 7 COOH terminal amino acids with litorin (Table 2) [10]. Each of these peptides is widely distributed in both the central nervous system (CNS) and peripheral tissues, especially in the gastrointestinal (GI) tract [8]. Numerous studies demonstrate these two peptides are involved in a wide range of physiological and pathophysiological processes which include: in the CNS...

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Bombesin marine toxin conjugates inhibit the growth of lung cancer cells

Cited by 19 publications

References 29 publications

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

Insights into bombesin receptors and ligands: Highlighting recent advances

Bombesin Receptor-Mediated Imaging and Cytotoxicity: Review and Current Status

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