α‐Fetoprotein positively regulates cytochrome <i>c</i>‐mediated caspase activation and apoptosome complex formation

Semenkova, Lidia; Dudich, Elena; Dudich, I.V.; Tokhtamisheva, Natalie; Tatulov, Edward; Okruzhnov, Yury; Garcı́a-Foncillas, Jesús; Palop-Cubillo, J.A.; Korpela, Timo

doi:10.1046/j.1432-1033.2003.03836.x

Cited by 38 publications

(34 citation statements)

References 48 publications

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“…The presence of humoral factors modifying tumor growth in mouse serum was shown previously [2,7]. Our results are in line with previous data on the effects of hemoglobin degradation products and α-fetoprotein inducing apoptosis of tumor cells [6,11]. Presumably, one of the humoral factors, participating in tumor growth, is the complex of the studied proteins.…”

Section: Resultssupporting

confidence: 92%

Biological activity of hemoglobin-containing complex isolated from blood serum of mice with Ehrlich carcinoma

et al. 2006

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Injection of hemoglobin-containing complex of serum proteins isolated from animals with Ehrlich carcinoma led to regression of intraperitoneally and intramuscularly transplanted Ehrlich carcinoma in male C57Bl/6 mice. The hemoglobin-containing complex of serum proteins disturbed cycle distribution of Ehrlich carcinoma cells and caused apoptosis of about 34.3% tumor cells. Addition of hemoglobin-containing serum protein complex into Ehrlich carcinoma incubation medium did not lead to the death of tumor cells and even slightly increased their proliferation.

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Section: Resultssupporting

confidence: 92%

Biological activity of hemoglobin-containing complex isolated from blood serum of mice with Ehrlich carcinoma

et al. 2006

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“…Hence, it should be feasible to detect remnants of both signal types on individual growth-regulating proteins such as AFP. The elegant studies by Dudich et al have revealed that AFP blocks apoptosis inhibition while promoting cell death effectors (caspases) in tumor and cell-free systems (Dudich et al, 2000;Semenkova et al, 2003;Dudich et al, 2006). On the basis of GenBank identification, an AA sequence resembling a Fas-like peptide stretch (AA #59-86) is readily detectable on domain I ( Figure 5E) of HAFP (39% identity; 23 AA in length).…”

Section: D) Oncogene Transcription and Expressionmentioning

confidence: 97%

“…Although AFP may not be the direct cause of the altered growth structures observed in birth defects, the belief is held that some shock/stress-induced conformational (variant) forms of this fetal protein may influence, modulate, or contribute to such events (Mizejewski, 2001a). Over the last two decades, reports have emerged that some of these HAFP forms can serve as dual regulators of growth, capable of either enhancement or inhibition of growth, in cancer as well as fetal cells (Mizejewski, 2002;Semenkova et al, 2003). Furthermore, AFP has been reported to promote growth via the protein kinase A pathway (Li et al, 2002b).…”

Section: Introductionmentioning

confidence: 99%

Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid Sequence

Mizejewski¹

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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The structure of alpha-fetoprotein (AFP) is presen-ted in light of AFP membership and position in the albuminoid gene family in comparison to other gene family members. Ontogenetic AFP gene expression is reviewed considering AFP mRNA presence in various tissues at different times during development. The multiple molecular variant forms of AFP are discussed in relation to published reports of AFP binding proteins and cell surface receptors. The atlas further shows AFP as a protein consisting of multiple peptide-cassettes consisting of amino acid (AA) sequence stretches matched to peptide segments on prohormones and biological response modifier proteins. Such AFP peptide segments could potentially serve as delivery agents which could target vascular, neuroendocrine, or gastrointestinal cells. A discussion follows in which peptide epitopes, extracellular matrix proteins, serine proteases, extracellular matrix, and cellular adhesion AA identity sites on AFP are considered. The AFP molecule is also viewed as a carrier/ transport protein based on AA sequence comparison of various proteins that bind hydropho-bic ligands and heavy metals similar to AFP binding of such components. An analysis of trans-cription factors, tumor suppressors, and AA-rich motifs follows, interfaced with dimerization and nuclear localization sequence matches identified on the AFP molecule. Emphasis is further placed upon homeodomain and apoptosis AA sequence identi-ties given that AFP serves as a fetal, phasespecific protein throughout embryogenesis, histogenesis, and organogenesis. AFP AA sequences are further presented as peptide identification sites for Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid SequenceMizejewski GJ Atlas Genet Cytogenet Oncol Haematol. 2010; 14(2) 170 growth factors, receptors, cytoskeletal proteins, and chemo-kines. A closing discussion summarizes the multi-ple and varied motifs of peptide sequences matched to AAs on each of AFP's three domains. This study indicates that short peptide segments, in addition to full-length AFP, and domain and subdomain fragments of AFP, could be employed as functional agents to help unravel the complexity of biological roles ascribed to human AFP.

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“…AFP is able to induce apoptosis in tumor cells (27,28). The molecular mechanisms are at least partly elucidated.…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin-associated proteins isolated from blood serum of Ehrlich carcinoma-bearing mice

Доненко

Ситдикова²,

Syrtsev³

et al. 2008

Int J Oncol

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Abstract. In the present study, we analyzed differential composition of blood serum from Ehrlich carcinoma-bearing and healthy male C57Bl/6 mice by isolating complexes of hemoglobin and other serum proteins by a proteomic approach (gel filtration, gel electrophoresis, and mass spectrometry). The hemoglobin fractions isolated from the serum of micebearing tumors contained several proteins with molecular weights of 15, 65, 68, and 100 kDa, while hemoglobin fractions isolated from the serum of healthy mice did not contain additional protein bands. These bands were identified by MALDI-TOF as haptoglobin, serum albumin, a homologue of α-fetoprotein, and hemoglobin-α. Ion exchange chromatography indicated complex formation of these proteins. Injection of hemoglobin-associated blood serum proteins (HAP) isolated from tumor-bearing animals, leads to tumor regression. Intraperitoneally injected HAP-induced apoptosis in Ehrlich carcinoma cells but not normal peritoneal cells and led to a complete regression of the ascitic or solid Ehrlich carcinoma. A one-year follow up of the animals did not reveal any signs of tumor growth. In conclusion, HAP might be a novel principle of tumor regression. The clinical relevance of these findings with Ehrlich carcinoma should be investigated in the future.

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α‐Fetoprotein positively regulates cytochrome c‐mediated caspase activation and apoptosome complex formation

Cited by 38 publications

References 48 publications

Biological activity of hemoglobin-containing complex isolated from blood serum of mice with Ehrlich carcinoma

Biological activity of hemoglobin-containing complex isolated from blood serum of mice with Ehrlich carcinoma

Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid Sequence

Hemoglobin-associated proteins isolated from blood serum of Ehrlich carcinoma-bearing mice

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